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Min-Jie Wang,1– 3 Jiayu Wang,4 Houdi Zhang,2,3 Fang-Bin Hao,1– 3 Gan Gao,1– 3 Si-Meng Liu,1– 3 Xiao-Peng Wang,1– 3 Jing-Jie Li,1– 3 Zheng-Xing Zou,2,3 Qing-Bao Guo,1– 3 He-Guan Fu,2,3 Yi-Qin Han,2,3 Cong Han,2,3 Lian Duan2,3 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurosurgery, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan; Cong Han, Department of Neurosurgery, Department of Neurosurgery, the Fifth Medical Centre (South Campus), Chinese PLA General Hospital, No. 8 Dong-Da Street, Fengtai District, Beijing, 100071, People’s Republic of China, Tel +86-10-66947389 ; +86-13466346163 ; +86-10-66947388, Fax +86-10-62177976, Email duanlian307@sina.com; hc82225@126.comBackground: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD.Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression.Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables.Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late–Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.Keywords: moyamoya disease, complement, Suzuki stage, nomogram

Shan-Mei Liu,1,* Qin Zhao,1,* Wen-Jun Li,2 Jian-Quan Zhao1 1Bayannur Hospital Department of Cardiology, Bayannur City, Inner Mongolia, 015000, People’s Republic of China; 2Tangshan Central Hospital, Tangshan, Hebei, 063008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Quan Zhao, Tel +13947818787, Email 1036908013@qq.comAbstract: Cardiovascular diseases represent a global health crisis, and understanding the intricate molecular mechanisms underlying cardiac pathology is crucial for developing effective diagnostic and therapeutic strategies. Mitsugumin-53 (MG53) plays a pivotal role in cell membrane repair, has emerged as a multifaceted player in cardiovascular health. MG53, also known as TRIM72, is primarily expressed in cardiac and skeletal muscle and actively participates in membrane repair processes essential for maintaining cardiomyocyte viability. It promotes k-ion currents, ensuring action potential integrity, and actively engages in repairing myocardial and mitochondrial membranes, preserving cardiac function in the face of oxidative stress. This study discusses the dual impact of MG53 on cardiac health, highlighting its cardioprotective role during ischemia/reperfusion injury, its modulation of cardiac arrhythmias, and its influence on cardiomyopathy. MG53’s regulation of metabolic pathways, such as lipid metabolism, underlines its role in diabetic cardiomyopathy, while its potential to mitigate the effects of various cardiac disorders, including those induced by antipsychotic medications and alcohol consumption, warrants further exploration. Furthermore, we examine MG53’s diagnostic potential as a biomarker for cardiac injury. Research has shown that MG53 levels correlate with cardiomyocyte damage and may predict major adverse cardiovascular events, highlighting its value as a biomarker. Additionally, exogenous recombinant human MG53 (rhMG53) emerges as a promising therapeutic option, demonstrating its ability to reduce infarct size, inhibit apoptosis, and attenuate fibrotic responses. In summary, MG53’s diagnostic and therapeutic potential in cardiovascular diseases presents an exciting avenue for improved patient care and outcomes.Keywords: Mitsugumin-53, MG53, cardiovascular disease, cell membrane repair, ischemia/reperfusion

Rui-Huan Gao,1,&ast; Boyang Liu,2,&ast; Ying Yang,1 Ruoxi Ran,1 Yidan Zhou,1,&ast; Song-Mei Liu1,&ast; 1Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, People’s Republic of China; 2Department of Computer Science and Engineering, Michigan State University, East Lansing, MI, USA&ast;These authors contributed equally to this workCorrespondence: Song-Mei Liu; Yidan Zhou, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei Province, 430071, People’s Republic of China, Email smliu@whu.edu.cn; Yzhou12@whu.edu.cnPurpose: Diabetic nephropathy (DN) is a common complication of type 2 diabetes mellitus (T2DM) that significantly impacts the quality of life for affected patients. Dyslipidemia is a known risk factor for developing cardiovascular complications in T2DM patients. However, the association between serum lipoprotein(a) (Lp(a)) and high-density lipoprotein cholesterol (HDL-C) with DN requires further investigation.Patients and Methods: For this cross-sectional study, we randomly selected T2DM patients with nephropathy (DN, n = 211) and T2DM patients without nephropathy (T2DM, n = 217) from a cohort of 142,611 patients based on predefined inclusion and exclusion criteria. We collected clinical data from the patients to identify potential risk factors for DN using binary logistic regression and machine learning. After obtaining the feature importance score of clinical indicators by building a random forest classifier, we examined the correlations between Lp(a), HDL-C and the top 10 indicators. Finally, we trained decision tree models with top 10 features using training data and evaluated their performance with independent testing data.Results: Compared to the T2DM group, the DN group had significantly higher serum levels of Lp(a) (p < 0.001) and lower levels of HDL-C (p = 0.028). Lp(a) was identified as a risk factor for DN, while HDL-C was found to be protective. We identified the top 10 indicators that were associated with Lp(a) and/or HDL-C, including urinary albumin (uALB), uALB to creatinine ratio (uACR), cystatin C, creatinine, urinary ɑ1-microglobulin, estimated glomerular filtration rate (eGFR), urinary β 2-microglobulin, urea nitrogen, superoxide dismutase and fibrinogen. The decision tree models trained using the top 10 features and with uALB at a cut-off value of 31.1 mg/L showed an average area under the receiver operating characteristic curve (AUC) of 0.874, with an AUC range of 0.870 to 0.890.Conclusion: Our findings indicate that serum Lp(a) and HDL-C are associated with DN and we have provided a decision tree model with uALB as a predictor for DN.Keywords: type 2 diabetes mellitus, diabetic nephropathy, high density lipoprotein cholesterol, lipoprotein(a), machine learning

An Wen,1,2 Er-Ling Leng,3 Wen-Feng Cao,1,2 Zheng-bing Xiang,1,2 Wei Rao,1,2 Wen Cai,1,2 Yong-Liang Zhou,1,2 Fan Hu,1,2 Ling-feng Wu,1,2 Ping Zhang,1,2 Shi-Min Liu1,2 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Shi-Min Liu, Department of Neurology, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No. 92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +791-8772-1401, Email aifeng420@163.comObjective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5– 6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person’s susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients.Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM.Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia.Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.Keywords: tuberculosis, tuberculous meningitis, anemia, risk factors, prediction

An Wen,1,2 Wen-Feng Cao,1,2 Shi-Min Liu,1,2 Yong-Liang Zhou,1,2 Zheng-Bing Xiang,1,2 Fan Hu,1,2 Ling-Feng Wu,1,2 Wen Cai,1,2 Er-Ling Leng3 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Er-Ling Leng, Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No.92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +86791-8772-1401, Email wenan666@sina.comObjective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics.Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM.Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy.Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.Keywords: tuberculous meningitis, tuberculosis, cranial nerve palsy, risk factors, prediction

Chang Xu,1 Kai Cheng,1 Xiao-Ling Wu,1 Heng Yap Tai,1 Ye-Mao Chai,1 Zhi-Wen Yang,1 Qian-Hui Sun,1 Xing-Hua Qiu,1 Xing-Yue Yang,1 Na Li,1 Yan Tan,2 Shao-Ming Liu,3 Wei Chen4 1College of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Na Li, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Tel +86 15210722947, Email 201901035@bucm.edu.cnPurpose: We aim to explore expression profiles of genes in SCDH of CPPS model rat relevant to pain and inflammation by RNA-Seq and to investigate the mechanism of anti-inflammatory and analgesic of EA.Methods: Thirty-six SD male rats were randomly divided into three groups (n = 12): sham operation, model, and EA. The rat CPPS model was established by injecting CFA into the ventral lobes of the prostate. The rats in EA group were treated at Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) for a total of 20 times, with a frequency of 2/100Hz. Mechanical allodynia, H&E staining and ELISA were used to detect the changes of pain threshold and tissue inflammation; RNA-Seq technique was used for profiling gene changes in SCDH and qRT-PCR was used for further validation.Results: Persistent mechanical allodynia and severe tissue inflammatory reaction both occurred in CPPS rats. After EA therapy, the pain sensitivity and inflammatory response of CPPS rats decreased significantly. RNA-Seq identified that a total of 46 DEGs were significantly up-regulated and 65 DEGs down-regulated after EA. GO enrichment showed that EA was mainly reflected in the regulation of the immune system by participating in the regulation of leukocyte, neutrophil cellular processes and cytokine metabolism. KEGG enrichment demonstrated that signal transduction and immune system were the most significant pathways. We further identified that the expressions of Pik3r2, Akt1, and Casp9 were significantly up-regulated and Jak2 and Stat3 down-regulated in the PI3K-AKT/JAK-STAT signal pathway.Conclusion: Our study revealed that immune and inflammatory responses are the main biological events that induce chronic pelvic pain in rats, and EA can exert anti-inflammatory and analgesic effects by regulating the expression of related genes on PI3K-AKT/JAK-STAT signal pathway in SCDH. This study provided putative novel targets of EA, which may have anti-inflammatory and analgesic effects of CPPS.Keywords: electroacupuncture therapy, chronic pelvic pain, anti-inflammatory and analgesia, RNA-seq technique, cytokine, spinal cord dorsal horn

Pu-Yuan Xing,1,* Shou-Zheng Wang,1,* Ju-Fang Shi,2 Le Wang,2 Zhou-Guang Hui,3 Jian-Song Ren,2 Shang-Mei Liu,4 You-Lin Qiao,5 Min Dai,2 Jun-Ling Li1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Ling Li; Ju-Fang Shi Email lijunling@cicams.ac.cn; shijf@cicams.ac.cnBackground: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients.Patients and Methods: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors.Results: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets.Conclusion: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.Keywords: non-small cell lung cancer, chemotherapy, neo-adjuvant chemotherapy, adjuvant chemotherapy, epidemiology

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator.

Cheng-Feng Luo,1,2 Ning Hou,2,3 Juan Tian,1,2 Mu Yuan,2,3 Shi-Ming Liu,1,2 Long-Gen Xiong,1,2 Jian-Dong Luo,2,3 Min-Sheng Chen1,2,41The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; 2Guangzhou Institute of Cardiovascular Disease, Guangzhou, People's Republic of China; 3Guangzhou Medical University, Guangzhou, People's Republic of China; 4Southern Medical University, Guangzhou, People's Republic of ChinaAbstract: Puerarin has multiple pharmacological effects and is widely prescribed for patients with cardiovascular diseases including hypertension, cerebral ischemia, myocardial ischemia, diabetes mellitus, and arteriosclerosis. We have successfully prepared puerarin-loaded solid lipid nanoparticles (Pue-SLNs) for oral administration. Pue-SLNs are prepared using monostearin, soya lecithin, and poloxamer 188. SLNs may alter the course of puerarin absorption predominantly to and through lymphatic routes and regions, presumably following a transcellular path of lipid absorption, especially by enterocytes and polar epithelial cells of the intestine. The alteration of absorption might influence the metabolic profile of puerarin when incorporated into SLNs. In the present study, we investigated the metabolic profile of puerarin in rat plasma and urine using rapid resolution liquid chromatography–tandem mass spectrometry after a single-dose intragastric administration of Pue-SLNs in comparison with puerarin suspension. Two glucuronidated metabolites of puerarin, puerarin-4΄-O-glucuronide and puerarin-7-O-glucuronide, were detected in rat plasma and urine after intragastric administration of Pue-SLNs, with the latter acting as the major metabolite. Similar results were found in rat plasma and urine after intragastric administration of puerarin suspension. The results suggest that incorporation of puerarin into SLNs does not change either the position of glucuronidation or the metabolic pathway of puerarin in rats.Keywords: puerarin, solid lipid nanoparticles, metabolic profiling

To study the neuroprotective effect of extract of Acanthopanax senticosus Harms against MPTP-induced mice model of Parkinson's disease and its mechanism. The Parkinson's disease mice model was induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Hydrochloride (MPTP-HCl, 30mg/kg daily for 5 days). High dose group and low dose group were medicated with extract of Acanthopanax senticosus Harms for 20 days, dose amounted to 182mg/kg and 45.5mg/kg daily respectively. The behavioral testing of mice was assessed using pole-climbing test. The levels of Dopamine (DA) and Homovanillic acid (HVA) in striatum were determined by Ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-ToF-MS). The levels of dopamine receptor 1 and 2 in striatum were assayed simultaneously with the help of immunohistochemical method. The level of Caspase-3 protein in substantia nigra was analyzed by Western Blot. From Day 5 during the administration of extract of Acanthopanax senticosus Harms, pole-climbing time in low and high dose group were significantly less than model group (p<0.05). Compared with model group, the DA level of striatum in low dose group was significantly higher (p<0.01), the number of dopamine receptor 1 and dopamine receptor 2-positive cells in low and high dose group were significantly less (p<0.05), the Caspase-3 protein level of substantia nigra in low and high dose group were significantly less (p<0.05). The neuroprotective effect of extract of Acanthopanax senticosus Harms may be able to protect C57BL/6 mice against MPTP-induced dopaminergic neuronal damage. [ABSTRACT FROM AUTHOR]

Background and purpose: 5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT3 receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect. Experimental approach: Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current ( Isc) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay ( elisa). Immunohistochemical techniques were used to study the expression of 5-HT3 receptors, somatostatin and somatostatin receptors in colonic tissue. Key results: In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT3 receptor antagonists enhanced 5-HT-induced increases in Isc. However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT3 receptor antagonists inhibited 5-HT-induced Δ Isc. Pretreatment with a somatostatin-2 (sst2) receptor antagonist in mucosa/submucosa preparations augmented 5-HT-induced Δ Isc. Combination of sst2 and 5-HT3 receptor antagonists did not cause further enhancement of 5-HT-induced Δ Isc. Moreover, both sst2 and 5-HT3 receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/submucosa preparations, an effect prevented by pretreatment with 5-HT3 receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT3 receptors on submucosal somatostatin neurons and of sst2 receptors on colonic mucosa. Conclusion and implications: Activation of neuronal 5-HT3 receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating immune cells are associated with tumor prognosis, although the type of immune cells responsible for local immune escape is still unknown. This study examined the relationship between gastric cancer survival and the density of immune cells, including CD8(+) T cells, CD20(+) B cells, and CD33(+)/p-STAT1(+) cells, which represent myeloid-derived suppressor cells, to evaluate the role of immune cells in the progression of gastric cancer. One hundred pathologically confirmed specimens were obtained from stage IIIa gastric cancers between 2003 and 2006 at Sun Yat-sen University Cancer Center, China. The density of tumor-infiltrating immune cells in tumor tissue was examined using immunohistochemical analysis. Clinicopathologic parameters and the survival rate were analyzed in relation to the density of immune cells. A high density of CD8(+) T cells and CD20(+) B cells was associated with a good clinical outcome, but a high density of CD33(+)/p-STAT1(+) cells was associated with a poor clinical outcome. Most importantly, the density of CD33(+)/p-STAT1(+) cells was an independent prognostic factor and inversely related to the infiltration of CD8(+) T cells. Although the infiltration of CD8(+) T cells and CD20(+) B cells is involved in the progression of gastric cancer, these data suggest that CD33(+)/p-STAT1(+) cells play a central role in the regulation of the local immune response, suggesting that CD33(+)/p-STAT1(+) cells might be therapeutic targets in gastric cancer. [ABSTRACT FROM AUTHOR]

Our purpose was to study the accuracy of using endorectal ultrasonography (ERUS) with sterile coupling gels filling the rectum in the preoperative T-staging of rectal carcinoma. A total of 189 patients with confirmed rectal carcinoma were recruited. All underwent ERUS and surgery within the week following sonography. EURS was performed by introducing sterile coupling gel into the rectum. Two radiologists looked at the images at the same time and agreed upon staging. Rectal carcinoma was staged from Tis to T4. The accuracy of T-staging by ERUS was 89.95%. The sensitivity, specificity, PPV and NPV for ERUS at different stages were calculated. For early stage (Tis and T1), these values were 93.62%, 97.89%, 93.62% and 97.89%, respectively. ERUS filling with sterile coupling gel in the rectum overcomes the pressure effect from a water bath and the restriction caused by tumor stenosis, thus, greatly improving the accuracy of T-staging. The examination is real-time, safe and inexpensive. [ABSTRACT FROM AUTHOR]

There are few reports on soluble epoxide hydrolase (sEH) structure-activity relationship studies using natural product-based scaffolds. In this study, we discovered that C-30 urea derivatives of glycyrrhetinic acid such as 33, rather than C-20/C-3 urea derivatives, possess in vitro sEH inhibitory capabilities. Furthermore, we explored the impact of stereoconfigurations at C-3 and C-18 positions, and glycosidic bonds at the 3-OH on the compound's activity. Consequently, a glycoside of 33, specifically 49Cα containing alpha-oriented mannose, exhibited promising in vivo efficacy in alleviating carrageenan-induced paw edema and acetic acid-induced writhing. Meanwhile, 49Cα demonstrated potential in mitigating acute pancreatitis by modulating the ratios of anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory dihydroxyeicosatrienoic acids (DHETs). The co-crystal structure of sEH in complex with 49Cα revealed that the N-tetrahydropyranylmethylene urea hydrogen bonded with the residues within the sEH tunnel, contrasting with the mannose component that extended beyond the tunnel's confines. Our findings highlight 49Cα (coded LQ-38) as a promising candidate for anti-inflammatory and analgesic effects, and pave the way for the future rational design of triterpenoid-based sEH inhibitors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Hua Liang reports financial support was provided by STI2030-Major Projects. Jian-Hua Liang reports financial support was provided by China's National Key Research and Development Program. Jian-hua Liang reports financial support was provided by China's National Natural Science Foundation. Jian-Hua Liang has patent #CN202410615904.9; CN202310704640.X pending to China National Intellectual Property Administration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Amino-berberine has remained underexplored due to limited biological evaluation and total synthesis approaches. In inflammation therapy, soluble Epoxide Hydrolase (sEH) is a promising target, yet natural scaffolds remain underutilized. Our study advances the field by redesigning natural compounds─berberine and sanguinarine─with strategic urea modifications and hydrogenated frameworks, creating novel sEH inhibitors with enhanced in vivo efficacy. Through total synthesis and structure-activity relationship studies of amino-berberine derivatives, chiral tetrahydroberberine ( R )-14i (coded LXZ-42 ) emerged as the most potent lead, with an IC 50 value of 1.20 nM. ( R )-14i showed reduced CYP enzyme impact, potent therapeutic effects on acute pancreatitis, no acute in vivo toxicity, and superior pharmacokinetic properties, with an oral bioavailability of 89.3%. Structural insights from crystallography of ( R )-14i bound to sEH revealed key interactions: three with the tetrahydroberberine framework and three hydrogen bonds with the urea group, highlighting ( R )-14i as a novel lead for sEH-targeted therapies in inflammation.

Background: Moyamoya disease (MMD) and moyamoya syndrome (MMS) are rare cerebrovascular conditions with unclear distinctions in clinical presentation and prognosis., Aim: This study assessed potential differences between MMD and MMS patients using real-world data on clinical manifestations, surgical outcomes, and stroke risk factors., Methods: This multicenter, retrospective cohort study examined patients with MMD or MMS treated at three tertiary academic hospitals in China, with a mean follow-up of 11.2 ± 3.1 years. Clinical differences were compared between MMD and MMS, and postoperative cerebrovascular events were compared between patients who underwent surgery and those with conservative management. Primary outcomes were postoperative ischemic and hemorrhagic strokes. Risk factors were evaluated via multivariate Cox regression analysis., Results: Of the 2565 patients, 2349 had MMD and 216 had MMS. After 1:1 propensity-score matching, no significant differences were observed between these two cohorts. Surgical patients had fewer cerebrovascular events than those who received conservative treatment (HR, 0.487; 95% CI, 0.334-0.711; p < 0.001). Preadmission modified Rankin scale scores > 2 (HR, 3.139; 95% CI, 1.254-7.857; p = 0.015) and periprocedural complications (HR, 8.666; 95% CI, 3.476-21.604; p < 0.001) were independent stroke risk factors in patients with MMD. Periprocedural complications (HR, 31.807; 95% CI, 10.916-92.684; p < 0.001) increased stroke risk in patients with MMS., Conclusions: This real-world study revealed substantial clinical overlap between MMD and MMS. Both groups derived significant benefits from surgical revascularization, suggesting distinction may not be necessary to guide surgical management decisions. Optimizing preoperative status and preventing periprocedural complications may improve outcomes in these rare cerebrovascular conditions., Trial Registration: This study has been registered in the Chinese Clinical trial registry (registration number: ChiCTR2200064160)., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Fusion proteins have the potential to become the new norm for targeted therapeutic treatments. Highly specific payload delivery can be achieved by combining custom targeting moieties, such as V HH domains, with active parts of proteins that have a particular activity not naturally targeted to the intended cells. Conversely, novel drug products may make use of the highly specific targeting properties of naturally occurring proteins and combine them with custom payloads. When designing such a product, there is rarely a known structure for the final construct which makes it difficult to assess molecular behaviour that may ultimately impact therapeutic outcome. Considering the time and cost of expressing a construct, optimising the purification procedure, obtaining sufficient quantities for biophysical characterisation, and performing structural studies in vitro, there is an enormous benefit to conduct in silico studies ahead of wet lab work. By following a repeatable, streamlined, and fast workflow of molecular dynamics assessment, it is possible to eliminate low-performing candidates from costly experimental work. There are, however, many aspects to consider when designing a novel fusion protein and it is crucial not to overlook some elements. In this work, we suggest a set of user-friendly, open-source methods which can be used to screen fusion protein candidates from the sequence alone. We used the light chain and translocation domain of botulinum toxin A (BoNT/A) fused with a selected V HH domain, termed here LC-H N -V HH , as a case study for a general approach to designing, modelling, and simulating fusion proteins. Its behaviour in silico correlated well with initial in vitro work, with SEC HPLC showing multiple protein states in solution and a dynamic protein shifting between these states over time without loss of material., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests to declare. This research was sponsored by Ipsen Bioinnovation. S.M. Liu was an employee of Ipsen at the time of the work & K.A. Bunting is an employee of Ipsen., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to compare cervical preparation with transcervical balloon to osmotic dilators for second-trimester procedural abortions., Study Design: We performed an unblinded, randomized, noninferiority trial of people undergoing second-trimester procedural abortion at 18 + 0 to 23 + 6 weeks' gestation. We randomized participants to either overnight osmotic dilators (Dilapan-S) or transcervical balloon (Foley). Both groups received overnight mifepristone and preprocedural misoprostol. We powered the study on mean difference in procedure duration, a noninferiority limit of 5 minutes. We compared preprocedure cervical dilation and the need for additional dilation and, using a 100-point visual analog scale, measured physician satisfaction and ease of procedure, and participant pain and satisfaction., Results: We recruited 32 participants at a single academic center. Although procedure time (minutes) was similar (balloon: 22.6 ± 8.9 vs Dilapan-S: 22.4 ± 12.8, p = 0.96), noninferiority was not met (mean difference, 0.2 minutes; 95% CI, -7.8 to 8.2). Cervical dilation >2 cm was more likely after Dilapan-S (100% vs 62.5%, p = 0.02). Placement was well tolerated with similar time (minutes) for insertion (balloon: 4.8 ± 1.0, Dilapan-S: 5.1 ± 2.3, p = 0.64) and maximum pain (median) with insertion (balloon 39 [5-78], Dilapan-S: 39 [0-100], p = 0.92). Pain immediately postinsertion was higher for Dilapan-S (33 [0-100] vs 18 [0-50], p = 0.046) and similar for maximum pain overnight, participant satisfaction, and likelihood to recommend. Complications were minor and similar between groups (p = 0.60)., Conclusion: While significantly more people with transcervical balloon required mechanical dilation, the difference in operative time was clinically negligible. The transcervical balloon was well tolerated and acceptable by participants., Implications: Clinicians experienced in mechanical dilation may consider a transcervical balloon as a lower-cost tool for second-trimester abortion cervical preparation., Clinical Trial Registration: ClinicalTrials.gov: NCT05099991., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Indirect revascularization is one of the main techniques for the treatment of Moyamoya disease. The formation of good collateral circulation is a key measure to improve cerebral blood perfusion and reduce the risk of secondary stroke, and is the main method for evaluating the effect of indirect revascularization. Therefore, how to predict and promote the formation of collateral circulation before and after surgery is important for improving the success rate of indirect revascularization in Moyamoya disease. Previous studies have shown that vascular endothelial growth factor, endothelial progenitor cells, Caveolin-1, and other factors observed in patients with Moyamoya disease may play a key role in the generation of collateral vessels after indirect revascularization through endothelial hyperplasia and smooth muscle migration. In addition, mutations in the genetic factor RNF213 have also been associated with this process. This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: To summarize notable recent research in adolescent reproductive health, particularly with respect to a rapidly changing legal landscape surrounding health services that significantly impact adolescent health., Recent Findings: Approval of the first over-the-counter contraceptive pill represented a major advance in adolescent reproductive health, which relied on research regarding its safety, efficacy, and potential to increase access for vulnerable groups. Despite this approval, disparities persist in equitable contraceptive access for adolescents of color and those from sexual and gender identity minorities. Legal changes in access to abortion care and parental involvement in reproductive health decision-making have presented significant challenges for young people across the U.S. Recent research points to the promise of telehealth abortion care and parental acceptance of confidentiality in adolescent reproductive healthcare. Misinformation remains a barrier to advancing adolescent reproductive health and points to continued opportunities for providers to create evidence-based online content., Summary: In this review, we discuss recent research regarding adolescent reproductive health and laws impacting the reproductive health of adolescents. As the legal landscape evolves, further research surrounding the effect of policy changes that both expand and restrict access to adolescent reproductive health services will be critical to advancing adolescent health., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Epidermal growth factor receptor ( EGFR ) and mesenchymal-epithelial transition ( MET ) gene mutations are well established in the pathogenesis of non-small cell lung cancer (NSCLC). However, there is limited understanding about the impact of rare variants, such as EGFR exon 20 insertion mutation ( EGFR ex20ins) and MET exon 14 skipping mutation ( MET ex14) in the Chinese population even though targeted therapies have been approved in China. We conducted a scoping review to assess the current available evidence of these two mutations in NSCLC in the Chinese population., Methods: Electronic searches were performed before November 2023. Two investigators independently collected data. Any discrepancies were resolved through discussion with a senior investigator., Results: We identified 111 studies, involving a total of 159,993 NSCLC Chinese patients. Of the 111 studies, 76 studies reported on EGFR ex20ins and 45 reported on MET ex14. When we evaluated the frequency from studies with at least 1,000 patients, the frequency of EGFR ex20ins ranged from 0.02-2.85% of all NSCLC patients and 0.56-6.90% of all EGFR mutations. The frequency of MET ex14 ranged from 0.08-1.38% of all NSCLC patients and 8.33-56.60% of all MET mutations. The treatments for NSCLC with EGFR ex20ins varied depending on the study, and all available treatments have limited therapeutic efficacy and a relatively poor prognosis, and fewer studies have examined the efficacy and effectiveness of treatments for NSCLC with MET ex14 mutation in the Chinese population., Conclusions: Despite the recent approval of three targeted therapies in China, there is still insufficient evidence regarding their optimal treatment and therapeutic efficacy for Chinese patients. Further large-scale studies are needed to establish links between these mutations and clinical features at baseline and following treatment. Furthermore, moving forward, the development of novel drugs will be essential to fulfill the clinical unmet needs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-528/coif). All authors report that this study was funded by Xi’an Janssen Pharmaceutical Ltd. X.G. and Y.W. were employees of Xi’an Janssen Pharmaceutical Ltd. during the study. The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Acute pain, defined as short-term pain arising from injury or other noxious stimuli, affects patient outcomes, quality of life, and healthcare costs. Safe, effective treatment of acute pain is essential in preventing increased morbidity, mortality, and the transition to chronic pain. In this review, we explore some of the latest therapeutic agents, formulations, combinations, and administration routes of drugs emerging in clinical practice in the USA for the treatment of acute pain. These agents include VX-548 (Suzetrigine), Cebranopadol, AAT-076, Combogesic intravenous (IV), sublingual ketamine, XG004 (naproxen/pregabalin conjugate), and HTX-011 (Zynrelef). We analyze the pharmacodynamics, pharmacokinetics, development status, and clinical implications of these drugs, emphasizing the importance of finding an agent that provides both a strong safety profile and effective relief from acute pain. Our findings show promise but also highlight the need for further large-scale research to allow these drugs to be utilized in a clinical context for patients experiencing acute pain., Competing Interests: Declarations Funding No funding was received for the preparation of this manuscript. Conflicts of Interest B.O., C.D., G.P., A.R., S.L., and S.D.B. declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Ethics Approval Not applicable for this review manuscript. Consent Not applicable. Authors’ Contributions Conceptualization: A.R., S.L. and S.D.B. Investigation: B.O., C.D., G.P. and A.R. Writing—original draft preparation: B.O., C.D., G.P. and A.R. Writing—review and editing: B.O., C.D., G.P., A.R., S.L. and S.D.B. Supervision: S.L. and S.D.B. Data availability All data generated or analyzed during this study are included in this published article. Code availability Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The outbreak and spread of African swine fever virus (ASFV) have caused considerable economic losses to the pig industry worldwide. Currently, to promote the development of effective ASF vaccines, especially subunit vaccines, more antigenic protein targets are urgently needed. In this work, six transmembrane proteins (I329L, E146L, C257L, EP153R, I177L, and F165R) were expressed in mammalian cell lines and screened with pig anti-ASFV serum. It was found that the E146L protein was an immunodominant protein antigen among the six selected proteins. Moreover, the E146L protein induced antibody responses in all immunized pigs. To gain insight into the antigenic characteristics of the E146L protein, three monoclonal antibodies (mAbs; 12H12, 15G1, and 15H10) were generated by immunizing BALB/c mice with the purified E146L protein. The epitopes of the mAbs were further finely mapped through a peptide fusion protein expression strategy. Finally, the epitopes of the mAbs were identified as 48 PDESSIAYMRFRN 61 of the mAb 12H12, 138 TLTGLQRII 146 of the mAb 15G1, and 30 GWSPFKYSKGNT 41 of the mAb 15H10. Furthermore, the epitope of mAb 15H10 was validated as the immunodominant epitope with ASFV-infected pig sera. The chemically synthesized mAb 15H10 epitope peptide (EP1) exhibited the most extensive immunoreactivity with artificially or naturally ASFV-infected pig sera. The epitope 15H10 is located on the surface of the E146L protein and is highly conserved. These findings provide insight into the structure and function of the E146L protein of ASFV., Competing Interests: Declarations Animal ethics All the experiments were performed strictly in accordance with the guidelines of care and use of laboratory animals by the Ministry of Science and Technology of the People’s Republic of China. The mouse and pig experimental protocols were approved by the Harbin Veterinary Research Institute (approval number: mouse experiment, 220110-02-GR; pig experiment, 230414-01-SW). All animals used in this study were carefully fed, and the suffering of the animals was minimized. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To explore the relevant factors associated with poor prognosis in patients suffering from chronic obstructive pulmonary disease (COPD) combined with pulmonary embolism (PE), and investigate the predictive value of the simplified pulmonary embolism severity index (sPESI) score on adverse outcomes in these patients. Methods: A total of 168 patients with COPD and PE who were treated at West China Hospital of Sichuan University from January 1, 2018, to December 30, 2020 were retrospectively included. Patients were divided into adverse outcome group and control group based on the occurrence of adverse outcomes [any of the following events: in-hospital death, intensive care unit (ICU) admission, and endotracheal intubation]. Correlation factors for poor prognosis were explored using multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was employed to assess the predictive value of the sPESI score for adverse outcomes in COPD patients with PE. Results: A total of 168 patients were studied, with an age of (73.4±10.4) years and 119 male (70.8%). In the adverse outcome group, there were 18 cases (10.7%), including 12 in-hospital deaths, 6 ICU admission, and 1 endotracheal intubation. The control group comprised 150 cases (89.3%). Statistically significant differences were observed between two groups regarding the proportion of patients with diabetes, nephrotic syndrome, severe pneumonia, respiratory failure and lower extremity edema, and the pulse, diastolic blood pressure, pulse oxygen saturation, lactate dehydrogenase and cholesterol levels (all P <0.05). Multivariate logistic regression analysis revealed that severe pneumonia, respiratory failure, lower extremity edema, and diastolic blood pressure<60 mmHg (1 mmHg=0.133 kPa) are correlative factors of adverse outcomes in patients with COPD complicated by PE [ OR (95% CI ) were 7.363 (1.053-51.772), 4.077 (1.030-16.133), 4.490 (1.131-17.832), and 8.060 (1.209-53.918), respectively, all P <0.05]. The sPESI score in the adverse outcome group was higher than that in the control group [ M ( Q 1 , Q 3 ), 2 (2, 2) vs 1 (1, 2) score, P =0.006]; the optimal cutoff value for sPESI score was 2 score, the sensitivity was 77.8%, the specificity was 54.0%, and the area under the curve (AUC) and 95% CI were 0.681 (0.554-0.809) based on the ROC curve analysis. Patients with sPESI≥2 score exhibited a 4.109-fold (95% CI : 1.292-13.063, P =0.017) increased risk of adverse prognosis compared to those with sPESI<2 score. Conclusions: Patients with COPD combined with PE have a higher incidence of adverse prognostic outcomes. Severe pneumonia, respiratory failure, lower limb edema, and diastolic pressure<60 mmHg are associated factors for poor prognosis. The sPESI score has some value in predicting adverse outcomes in COPD patients with PE.

In this study, the liquid culture system of Pleurotus nebrodensis mycelium with high yield were established by using orthogonal experiments. Results indicated a 58.08 % increase in mycelium biomass and a 2.22 % increase in polysaccharide content after condition optimization. Experiments showed that the extracted polysaccharides have significant antioxidant and anti-exercise fatigue activities. They could effectively scavenge DPPH, ABTS, hydroxyl free radicals and superoxide anaion, prolong weight-loaded swimming time in mice, reduce levels of MDA, LD, and LDH in serum, enhance SOD activity, as well as increase hepatic and muscle glycogen reserves. The mechanism may be attributed to the activation of the Nrf2/Keap1 signaling pathway, inhibition of oxidative stress, and subsequent exerting anti-fatigue effects. The results in this work provides new avenue for easily accessible natural polysaccharide resources with a very convenient approach, which is beneficial for the development of anti-fatigue functional foods for public consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Currently, there are no specific drugs for treating acute pancreatitis. Soluble epoxide hydrolase (sEH) inhibitors show promise, but face challenges like low blood drug concentrations and potential adverse effects on CYP enzymes and the human ether-a-go-go-related gene (hERG). In this study, an approach involving scaffold hopping and structure-activity guided optimization was employed to design a series of phenylquinoline-based sEH inhibitors. Among these compounds, DJ-53 exhibited potent in vitro and in vivo effects in alleviating pain and reducing inflammation. The in vivo mechanism of action involved inhibiting sEH enzyme activity, thereby increasing levels of anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreasing levels of proinflammatory dihydroxyeicosatrienoic acids (DHETs). Importantly, DJ-53 showed exceptional oral bioavailability and pharmacokinetics, while avoiding inhibition of CYP enzymes or the hERG channel. These results highlight DJ-53's potential as a new lead compound for anti-inflammatory and analgesic applications and provide a safe and effective scaffold for developing sEH inhibitors.

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Hua Liang reports financial support was provided by National Key Research and Development Program of China. Nothing to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Rationale: Cerebral infarction is a common ischemic cerebrovascular disease, associated with high rates of morbidity, disability, and recurrence, that can seriously affect patient physical and mental health, as well as quality of life. Carotid artery stenosis is an independent risk factor of cerebral infarction. Following rapid developments in interventional technology and materials science, carotid artery stenting has arisen an important treatment option for carotid artery stenosis. However, surgery is associated with complications, such as postoperative hyperperfusion syndrome, which poses a serious threat to the life and health of patients. Staged angioplasty (SAP), that is, one-time revascularization of the carotid artery stenting, is divided into 2 stages. This method reduces the occurrence of hyperperfusion syndrome after stenting by increasing the ipsilateral cerebral blood flow in stages and gradually increasing the cerebral perfusion pressure., Patient Concerns: Herein, we present 2 cases of elderly patients with severe carotid artery stenosis who underwent SAP to prevent hyperperfusion syndrome., Diagnoses: The final diagnosis was based on cervical vascular color Doppler ultrasonography, cervical vascular magnetic resonance angiography, and cerebral vascular digital subtraction angiography., Intervention: Both patients with severe carotid artery stenosis underwent a staged intravascular intervention., Outcomes: Both patients were followed up for 1 year, with neither developing any new cerebral infarction or recurrent stent restenosis., Lessons: When treating SAP, it is crucial to consider that patients with unstable carotid plaques may not be suitable for staging. Additionally, during phase II carotid stenting, it is important to assess any changes in the arterial morphology and select the appropriate device accordingly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)