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Han-Song Sheng,1 Fang Shen,2 Nu Zhang,1 Li-Sheng Yu,1 Xiang-Qi Lu,1 Zhe Zhang,1,3 Huang-Yi Fang,1,3 Ling-Li Zhou,4 Jian Lin11Department of Neurosurgery, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Orthopedic Surgery‘s Spine Division, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, People’s Republic of China; 3School of the 2nd Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Pathology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaBackground: Although meningiomas are common intracranial tumors, multiple meningiomas (MMs) are rare entities in patients without neurofibromatosis type 2. Previous studies suggest most sporadic MMs are of monoclone in origin.Objective: To elucidate the clonal relationship between two sporadic meningiomas from the same patient by using the next-generation sequencing (NGS) platform.Methods: Two MMs, located frontally and parietally on the right side, were surgically removed from a 52-year-old male. Pathological examinations and whole exome sequencing were performed on tumor samples, followed by Sanger sequencing validation.Results: MMs were diagnosed as secretory and fibrous subtypes, respectively, on histology (WHO grade I) and tumor DNA exhibited distinctive somatic mutation patterns. Specifically, the secretory subtype carried more single nucleotide variant while the fibrous subtype had much higher copy number variation. Besides, the two tumors demonstrated different mutation profiles in predisposing genes and known driver mutations. For example, the secretory subtype had missense mutations in TRAF7 and KLF4, while the fibrous subtype had frameshift deletion of NF2 gene in addition to copy number loss of NF2 and SMARCB1, genetic events that have already been associated with the development of meningiomas. Significantly mutated gene analysis revealed novel mutations of LOC729159 in the secretory subtype and RPGRIP1L and DPP6 in the fibrous subtype. Sanger sequencing validated important point mutations in TRAF7 (c.1678G>A, p.G560S), KLF4 (c.1225A>C, p.K409Q) and CDH11 (c.169T>G, p.W57G).Conclusion: Our data suggest the two meningiomas might develop independently in this patient and molecular subtyping by NGS is a valuable supplement to conventional pathology. Further study is needed to ascertain whether these novel genetic events are tumorigenic or simply passenger mutations, as well as their clinical implicationsKeywords: multiple meningiomas, whole exome sequencing, secretory meningioma, fibrous meningioma, TRAF7, NF2

Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug–drug interactions (DDIs) when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.Methods: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.Results: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John’s wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C>A), species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.Conclusion: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring. Keywords: clopidogrel, drug–drug interactions, drug metabolism, drug transporter, genotype, pharmacokinetics, polypharmacy, pharmacogenetics, P2Y12 receptor inhibitors, risk management

Chu-Han Gao,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities), socioeconomic, and cultural factors. Levofloxacin (LVX) is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.Methods: Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.Results: In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be associated with sample size and administration route. Children younger than 5 years cleared LVX nearly twice as fast as adults. Patients in intensive care receiving LVX therapy showed significant pharmacokinetic differences compared with healthy subjects. Creatinine clearance explained most of the population variance in the plasma clearance of LVX. Switching from intravenous to oral delivery of LVX had economic benefits. Addition of tamsulosin to the LVX regimen was beneficial for patients with bacterial prostatitis because tamsulosin could increase the maximal concentration of LVX in prostatic tissue. Coadministration of multivalent cation-containing drugs and LVX should be avoided. For patients receiving warfarin and LVX concomitantly, caution is needed regarding potential changes in the international normalized ratio; however, it is unnecessary to seek alternatives to LVX for the sake of avoiding drug interaction with warfarin. It is unnecessary to proactively reduce the dose of cyclosporin or tacrolimus when comedicated with LVX. Transporters such as organic anion-transporting polypeptide 1A2, P-glycoprotein, human organic cation transporter 1, and multidrug and toxin extrusion protein 1 are involved in the pharmacokinetics of LVX.Conclusion: Personalized LVX therapeutics are necessary for the sake of better safety, clinical success, and avoidance of resistance. New findings regarding individual dosing of LVX in special patient populations and active transport mechanisms in vivo are opening up new horizons in clinical practice.Keywords: drug interactions, fluoroquinolone resistance, individual dosing, patient complexity, personalized medicine, pharmacokinetics, pharmacodynamics, therapeutics

Yi-Ting Zhou,1 Lu-Shan Yu,2 Su Zeng,2 Yu-Wen Huang,1 Hui-Min Xu,1 Quan Zhou11Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of ChinaBackground: Coadministration of 1,4-dihydropyridine calcium channel blockers (DHP-CCBs) with statins (or 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) is common for patients with hypercholesterolemia and hypertension. To reduce the risk of myopathy, in 2011, the US Food and Drug Administration (FDA) Drug Safety Communication set a new dose limitation for simvastatin, for patients taking simvastatin concomitantly with amlodipine. However, there is no such dose limitation for atorvastatin for patients receiving amlodipine. The combination pill formulation of amlodipine/atorvastatin is available on the market. There been no systematic review of the pharmacokinetic drug–drug interaction (DDI) profile of DHP-CCBs with statins, the underlying mechanisms for DDIs of different degree, or the corresponding management of clinical risk.Methods: The relevant literature was identified by performing a PubMed search, covering the period from January 1987 to September 2013. Studies in the field of drug metabolism and pharmacokinetics that described DDIs between DHP-CCB and statin or that directly compared the degree of DDIs associated with cytochrome P450 (CYP)3A4-metabolized statins or DHP-CCBs were included. The full text of each article was critically reviewed, and data interpretation was performed.Results: There were three circumstances related to pharmacokinetic DDIs in the combined use of DHP-CCB and statin: 1) statin is comedicated as the precipitant drug (pravastatin–nimodipine and lovastatin–nicardipine); 2) statin is comedicated as the object drug (isradipine–lovastatin, lacidipine–simvastatin, amlodipine–simvastatin, benidipine-simvastatin, azelnidipine–simvastatin, lercanidipine–simvastatin, and amlodipine–atorvastatin); and 3) mutual interactions (lercanidipine–fluvastatin). Simvastatin has an extensive first-pass effect in the intestinal wall, whereas atorvastatin has a smaller intestinal first-pass effect. The interaction with simvastatin seems mainly driven by CYP3A4 inhibition at the intestinal level, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition. The interaction of CYP3A4 inhibitor with simvastatin has been more pronounced compared with atorvastatin. From the current data, atorvastatin seems to be a safer CYP3A4-statin for comedication with DHP-CCB. There is no convincing evidence that amlodipine is an unusual DHP-CCB, either as a precipitant drug or as an object drug, from the perspective of CYP3A4-mediated drug metabolism. Amlodipine may have interactions with CYP3A5 in addition to CYP3A4, which may explain its particular characteristics in comparison with other DHP-CCBs. The degree of DDIs between the DHP-CCB and statin and the clinical outcome depends on many factors, such as the kind of statin, physicochemical proprieties of the DHP-CCB, the dose of either the precipitant drug or the object drug, the sex of the patient (eg, isradipine–lovastatin), route of drug administration (eg, oral versus intravenous nicardipine–lovastatin), the administration schedule (eg, nonconcurrent dosing method versus concurrent dosing method), and the pharmacogenetic status (eg, CYP3A5-nonexpressers versus CYP3A5-expressers).Conclusion: Clinical professionals should enhance risk management regarding the combination use of two classes of drugs by increasing their awareness of the potential changes in therapeutic efficacy and adverse drug reactions, by rationally prescribing alternatives, by paying attention to dose adjustment and the administration schedule, and by review of the appropriateness of physician orders. Further study is needed – the DDIs between DHP-CCBs and statins have not all been studied in humans, from either a pharmacokinetic or a clinical perspective; also, the strength of the different pharmacokinetic interactions of DHP-CCBs with statins should be addressed by systematic investigations.Keywords: CYP3A4, 1,4-dihydropyridine, drug–drug interactions, HMG-CoA reductase inhibitors, myopathy, polypharmacy, physicochemical phenomena, prescription auditing

Wei Li,1 Su Zeng,2 Lu-Shan Yu,2 Quan Zhou31Division of Medical Affairs, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Omeprazole, a proton pump inhibitor (PPI), is widely used for the treatment of dyspepsia, peptic ulcer, gastroesophageal reflux disease, and functional dyspepsia. Polypharmacy is common in patients receiving omeprazole. Drug toxicity and treatment failure resulting from inappropriate combination therapy with omeprazole have been reported sporadically. Systematic review has not been available to address the pharmacokinetic drug-drug interaction (DDI) profile of omeprazole with adverse consequences, the factors determining the degree of DDI between omeprazole and comedication, and the corresponding clinical risk management.Methods: Literature was identified by performing a PubMed search covering the period from January 1988 to March 2013. The full text of each article was critically reviewed, and data interpretation was performed.Results: Omeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, nelfinavir, atazanavir, rilpivirine, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation. Meanwhile, low efficacy of omeprazole treatment would be anticipated, as omeprazole elimination could be significantly induced by comedicated efavirenz and herb medicines such as St John's wort, Ginkgo biloba, and yin zhi huang. The mechanism for DDI involves induction or inhibition of cytochrome P450, inhibition of P-glycoprotein or breast cancer resistance protein-mediated drug transport, and inhibition of oral absorption by gastric acid suppression. Sometimes, DDIs of omeprazole do not exhibit a PPI class effect. Other suitable PPIs or histamine 2 antagonists may be therapeutic alternatives that can be used to avoid adverse consequences. The degree of DDIs associated with omeprazole and clinical outcomes depend on factors such as genotype status of CYP2C19 and CYP1A2, ethnicity, dose and treatment course of precipitant omeprazole, pharmaceutical formulation of object drug (eg, mycophenolate mofetil versus enteric-coated mycophenolate sodium), other concomitant medication (eg, omeprazole-indinavir versus omeprazole–indinavir–ritonavir), and administration schedule (eg, intensified dosing of mycophenolate mofetil versus standard dosing).Conclusion: Despite the fact that omeprazole is one of the most widely prescribed drugs internationally, clinical professionals should enhance clinical risk management on adverse DDIs associated with omeprazole and ensure safe combination use of omeprazole by rationally prescribing alternatives, checking the appropriateness of physician orders before dispensing, and performing therapeutic drug monitoring.Keywords: administration schedule, drug interactions, drug toxicity, herb–drug interactions, omeprazole, pharmacokinetics, polypharmacy, prescription auditing, risk management, treatment failure

This study investigated whether previous contact with mental illness affected the attitudes to mental illness (AMI) of general student nurses in Hong Kong -- the contact hypothesis. We employed a quasi-experimental design. We compared the attitudes to mental illness of students who had previous contact with mental illness through having taken a psychiatric secondment with those who had not taken a psychiatric secondment. Also, we compared the AMI of: students who had taken other courses related to mental illness with those who had not; those who had a family history of mental illness with those who had not; and those who lived with a mentally ill relative with those who did not. We found that previous contact with mental illness had no significant effect on the attitudes to mental illness of the students. In other words our findings do not support the contact hypothesis. Our sample expressed positive general attitudes to mental illness when presented with general issues about mental illness. However, their attitudes were less positive when presented with specific issues about mental illness that might impinge upon their daily lives. We discuss the implications of these findings for mental health nursing practice, education and research. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD)., Methods: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot., Results: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01)., Conclusion: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aims to evaluate the application value in neurological outcome of cerebral regional oxygen saturation (CrSO 2 ) and amplitude-integrated electroencephalography (aEEG) monitoring during neonatal extracorporeal membrane oxygenation (ECMO) courses., Methods: We retrospectively analyzed 18 neonates receiving veno-arterial ECMO (V-A ECMO) support at our hospital from July 2021 to December 2022. Continuous monitoring of CrSO 2 and brain electrical activity was conducted using near-infrared spectroscopy (NIRS) and aEEG throughout the ECMO treatment. We collected and analyzed related clinical data., Results: Among the 11 survivors, 5 were categorized as the normal group (N group) and 6 as the abnormal group (AN group) based on post-ECMO brain MRI outcomes. The N group exhibited shorter time percentage of significant CrSO 2 reduction (> 25% from baseline or absolute value < 40%), better fractional tissue oxygen extraction (FTOE) rates, and more stable mean percentage changes in CrSO 2 compared to the AN group. Neonates in the N group predominantly showed mildly abnormal aEEG readings, with one patient displaying disrupted sleep-wake cycles. This particular patient also had more significant CrSO 2 reduction and poorer FTOE compared to others in the N group. Additionally, the Test of Infant Motor Performance (TIMP) scores indicated hypoevolutism in this patient before discharge, while others in the N group had normal TIMP scores. In the AN group, 4 exhibited moderate and 2 severe aEEG abnormalities; 5 had hypoevolutism TIMP scores, and 1 with moderate aEEG abnormalities maintained a normal TIMP score, exhibiting lesser CrSO 2 reduction and improved FTOE., Conclusion: CrSO 2 and aEEG monitoring show potential as routine assessments for neurological outcomes during neonatal ECMO. In our cohort, a tendency was observed where neonates with greater reductions in CrSO 2 and more severe aEEG abnormalities experienced poorer neurological outcomes., (© 2024. The Author(s).)

Objective: To investigate the possible pathogenesis and possible risk factors of tinnitus related to female menopause. Methods: From April 2016 to October 2016, 59 female patients with menopausal syndrome were diagnosed in the menopause comprehensive management clinic. Tinnitus and menopause questionnaires were conducted, based on whether having tinnitus, those patients were divided into two groups: tinnitus group and no tinnitus group. Age, body mass index (BMI), Kupperman menopausal index (KMI) score, follicle-stimulating hormone (FSH) level of patients in the two groups were analyzed. Menopausal symptoms, related medical history and possible related factors of tinnitus were statistically analyzed. Results: A total of 59 cases were collected, 22 of which were accompanied by tinnitus. The incidence of idiopathic tinnitus was 35.1% (20/57) because 2 cases of thyroid related tinnitus with clear etiology were removed. Complete data were obtained from 17 of 20 patients with idiopathic tinnitus and 26 of 37 patients without tinnitus. Age, BMI, menopause KMI score, hormone level, menopause symptoms and possible factors related to tinnitus were statistically analyzed between the two groups, and the incidence of headache was statistically different between the two groups ( χ 2 =9.098, P =0.003), but no other factors were statistically significant( P >0.05). The severity of insomnia and tinnitus were further analyzed ( χ 2 =2.841, P =0.417), and there was no significant difference between the two groups. Conclusion: Headache history may be one of the high risk factors for the occurrence of menopausal tinnitus.

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop-mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 10 3  genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point-of-care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources., (© 2024 Wiley Periodicals LLC.)

Primary ectopic meningioma of the middle ear is relatively rare in clinical practice. It is often difficult to distinguish it from chronic otitis media or otitis media with effusion due to its similar and atypical clinical symptoms. We report a case of epithelial tympanic ectopic meningioma with the main complaints of otalgia, aural fullness, and hearing loss. It was accidentally discovered during tympanotomy due to the symptoms of recurring refractory secretory otitis media. This article briefly reviews the relevant literature in recent years, summarizes the characteristics of primary ectopic tympanic meningioma with intact tympanic membrane, and emphasizes the diagnosis and treatment strategy of the middle ear mass., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The speciation of heavy metals in soil is an important factor determining their bioavailability and toxicity, and it is crucial for the scientific assessment of ecological risks posed by heavy metals in soils of typical carbonate areas with high geological background in southwest China. In order to investigate the distribution of speciation of heavy metals in soils of carbonate rock with high geological background, we selected a typical carbonate rock distribution area in Guizhou Province and used the second national soil survey plots as sampling units. A total of 309 topsoil samples were collected from farmland. The improved Tessier seven-step sequential extraction method was used to analyze the seven chemical forms of heavy metals:water-soluble (F1); exchangeable (F2); carbonate-bound (F3); weakly organic-bound (F4); iron-manganese oxide-bound (F5); strongly organic-bound (F6); and residual (F7) forms of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). The study found that the residual forms of heavy metals As, Cu, Hg, Ni, Pb, and Zn in the soil accounted for more than 50%, the effective components (F1-F3) accounted for less than 5%, and the potential biological effective components (F4-F6) were less than 45%, indicating low reactivity and low ecological risk. The effective and potentially bioavailable components of Cd accounted for 55.49% and 29.37%, respectively, which were much higher than those of other heavy metals. The ecological risk based on the speciation of heavy metals in the soil was much lower than that based on the total content of heavy metals. The stepwise regression equations could effectively establish the relationship between the bioavailable and potentially bioavailable fractions of Cd, Cu, and Pb and their influencing factors. Total heavy metal contents and pH value were important factors influencing the speciation of heavy metals in soils of carbonate rock with high geological background areas. The enrichment of heavy metal elements in the residual fraction was influenced by long-term zinc smelting activities and the weathering of carbonate rocks into soil. Soil organic matter (OM) and oxide content had a relatively small influence on the speciation of heavy metals in the soil.

Objective: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB)., Methods: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R)., Results: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05)., Conclusion: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.

Mechanobiology is a cornerstone in physiology. However, its role in biomedical applications remains considerably undermined. In this study, we employed cell membrane vesicles (CMVs), which are currently being used as nanodrug carriers, as tactile cues for mechano-regulation of collective cell behaviors. Gliomas, which are among the most resilient brain tumors and have a low patient survival rate, were used as the cell model. We observed that mechanical responses due to the application of glioma- or microglia-derived CMVs resulted in the doubling of the traction stress of glioma cell collectives with a 10-fold increase in the CMV concentration. Glioma-CMVs constrained cell protrusions and hindered their collective migration, with the migration speed of such cells declining by almost 40% compared to the untreated cells. We speculated that the alteration of collective polarization leads to migration speed changes, and this phenomenon was elucidated using the cellular Potts model. In addition to intracellular force modulation and cytoskeletal reorganization, glioma-CMVs altered drug diffusion within glioma spheroids by downregulating the mechano-signaling protein YAP-1 while also marginally enhancing the associated apoptotic events. Our results suggest that glioma-CMVs can be applied as an adjuvant to current treatment approaches to restrict tumor invasion and enhance the penetration of reagents within tumors. Considering the broad impact of mechano-transduction on cell functions, the regulation of cell mechanics through CMVs can provide a foundation for alternative therapeutic strategies.

To study the sources and potential risks of heavy metals in soils of characteristic agricultural product producing areas is of great significance for the scientific management and safe utilization of soil and crop resources. The contents of heavy metals As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the 254 surface soil samples collected from the Heze oil peony planting area were determined. The content characteristics and correlation of heavy metals were analyzed using multivariate statistical methods. The sources of heavy metals in topsoil were analyzed using I geo , PMF, and PCA/APCS. The ecological risks of the eight heavy metals were assessed through the potential ecological risk index (PERI). The results showed that the average contents of seven heavy metals in the soil were basically consistent with the background values of soil elements in Heze City, except that the average value of Cd was 1.44 times higher than the background value in Heze City. Correlation analysis and cluster analysis revealed that Pb, Hg, and Cd elements in the soil were greatly affected by human activities in the later period. The sources of eight heavy metals in the study area were natural sources, agricultural fertilizer sources, industrial coal sources, and domestic transportation sources, with the contribution rates of 81.31%, 15.45%, 2.74%, and 0.50%, respectively; 84.25% of the sites in the study area were at slight ecological risk, whereas the moderate risk and strong risk sites accounted for 14.96% and 0.79%, respectively. Among them, Cd and Hg were the dominant elements of ecological risk in the study area.

Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta., Methods: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected., Results: The heterozygous mutation of the 26 exon c.1922&#95;1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala., Conclusion: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922&#95;1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss., Level of Evidence: Level 4., (Copyright © 2023 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

Background: Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients., Methods: Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5 kg/m 2 ., Results: A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18-92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure (6.3%, p = 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025-1.786, p = 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015-1.876, p = 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050-4.048, p = 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 × 10 3 /μL, p = 0.049) than the nonobese group., Conclusion: In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in this work., (Copyright © 2022. Published by Elsevier B.V.)

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross-tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time-series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2023 The Authors. GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

Objective: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM., Methods: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage., Results: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN., Conclusion: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To reclassify the flat type sudden deafness according to the types of audiogram shape, and to explore the correlation between different pattern of hearing loss and prognosis. Methods: All of 1 024 patients with unilateral sudden deafness (492 males and 532 females, aged from 19 to 65 years, with an average age of 41.2 years old) admitted to 33 hospitals nationwide from August 2007 to October 2011 were divided into four types according to Chinese Guideline of Sudden Deafness(2015): low-frequency, high-frequency, flat and total deafness. Then, 402 patients with flat type sudden deafness were further divided into ascending type, descending type and consistent type according to the audiogram shapes. First, we compared the clinical characteristics and prognosis among these three subtypes of flat deafness, then compared the clinical characteristics and prognosis between ascending flat deafness and low-frequency deafness, descending flat deafness and high-frequency deafness, consistent flat deafness and total deafness, explored the factors related to the prognosis of flat deafness. SPSS 21.0 software, ANOVA, χ 2 test, t -test and Logistic regression were used to analyze the data. Results: The cure rates of flat ascending, flat descending and flat consistent sudden deafness groups were 70.7%, 17.1% and 34.0% respectively, with a statistically significant difference (χ 2 =33.984, P <0.001); However, there was no significant difference in age, sex and affected side (all P >0.05). The independent related factors for the recovery of flat type sudden deafness were as follows: whether there was dizziness [ OR =0.459; 95% confidence interval ( CI): 0.271-0.777], the type of audiogram shape ( OR =0.721; 95% CI : 0.530-0.981), and days from onset to therapy ( OR =0.903, 95% CI : 0.835-0.978), all of which had P values<0.05. There was no significant difference in the cure rates between ascending flat sudden deafness and low-frequency descending sudden deafness, descending flat sudden deafness and high-frequency descending sudden deafness (all P >0.05). The pure tone average(PTA) of flat consistent sudden deafness and total deafness were (69.1±18.9) and (101.7±17.7) dB HL, respectively, with a statistically significant difference ( t =20.890, P <0.001), and the cure rates were 34.0% and 14.5%, respectively, with a statistically significant difference (χ 2 =29.012, P <0.001). Conclusion: According to the audiogram shape, the flat type sudden deafness can be further divided into ascending flat sudden deafness, descending flat sudden deafness and consistent flat sudden deafness, which can more effectively evaluate the prognosis. The cure rate of ascending flat sudden deafness is similar to that of low-frequency sudden deafness, and the prognosis is well; The cure rate of descending flat sudden deafness is similar to that of high-frequency descending sudden deafness, and the prognosis is poor. The cure rate of consistent flat sudden deafness is higher than that of total deafness. PTA plays an important role in the prognosis of consistent flat sudden deafness and total deafness. Total deafness can be regarded as a single type of sudden deafness.

This study used both the element occurrence form analysis and the chronic health risk assessment method to investigate the accumulation characteristics of heavy metals in the soil-crop system and the health risk assessment of agricultural products in northeastern Yunnan, which is a typical area of Southwest China where heavy metals are enriched in soil. Based on the study of 1137 groups of agricultural products and corresponding root soils, the results showed that the soil cadmium (Cd) and lead (Pb) in the lead-zinc ore concentration area were higher than the risk-intervention values of the "Soil Environmental Quality Risk control standard for soil contamination of agricultural land" (GB 15618-2018), whereas the soil Cd in the other parent material areas was within the screening-intervention buffer zone, and Pb was below the minimum risk-screening value. According to the National Food Safety Standard of China (GB 2762-2017), the heavy metal Cd in potatoes and soybeans in the area seriously exceeded the standard, the heavy metal Pb in tartary buckwheat and walnut exceeded the limit value, and the exceeding rate of heavy metal Cd in crops from these parent material areas showed: clastic rock>basalt>lead-zinc ore>carbonate ≈ Quaternary sedimentary>sand (mud) rock. According to the U.S. Environmental Protection Agency's assessment method for the chronic health risk of heavy metal intake by humans, the grains and potatoes, staple foods, and fruits had low chronic health risks of heavy metal intake. Agricultural products from the parent material area of clastic rock, sand (mud) rock, Quaternary sedimentary, and lead-zinc ore concentration showed health risks; with the change in soil physical and chemical properties and the increase in the types of edible crops, the risk will gradually increase. Based on this research, it is urgent to carry out real-time monitoring of agricultural products in the area.

Enterovirus A71 (EV-A71) is an emerging enterovirus that can cause neurological complications. Enhanced serum IL-1β levels were observed in EV-A71 patients with severe neurological symptoms. However, the roles of sensors in enterovirus-induced IL-1β production are unclear. In this study, we identified that pattern recognition receptors, including RIG-I, TLR3, and TLR8, are implicated in EV-A71-triggered IL-1β release in human macrophages. EV-A71 infection results in caspase-1 and caspase-8, which act as regulators of EV-A71-induced NLRP3 and RIG-I inflammasome activation. Moreover, knockdown of the expression of TLR3 and TLR8 decreased the released IL-1β in an NLRP3-dependent manner. Since TLR3 and TLR8 ligands promote NLRP3 inflammasome activation via caspase-8, the alternative pathway may be involved. In summary, these results indicate that activation of the NLRP3 and RIG-I inflammasomes in EV-A71-infected macrophages is mediated by caspase-1 and caspase-8 and affected by TLRs, including TLR3 and TLR8., (© 2022. The Author(s).)

Objective: To investigate the peripheral blood inflammatory markers including white blood cell count (WBC), monocytes, neutrophils, lymphocytes, platelets, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), high-density lipoprotein(HDL-C), low-density lipoprotein and fibrinogen (FIB) in Ménière's disease (MD) patients with and without migraine, and to explore the relationship between the inflammatory response with MD and migraine. Methods: The general physical condition, clinical manifestations, pure-tone audiometry, and peripheral blood inflammatory markers of 92 unilateral MD patients who were hospitalized in Peking University People's Hospital for surgical treatment from January 2017 to January 2021 were continuously collected. Meanwhile, 50 healthy controls matched with age and sex were included, and their general physical conditions and peripheral blood inflammatory markers were also collected. This study consisted of two parts. First, the differences in epidemical characteristics and peripheral blood inflammatory markers between MD patients and healthy controls were compared by univariate analysis. Second, all 92 MD patients were divided into two subgroups according to whether they were accompanied by migraine. The clinical characteristics and peripheral blood inflammatory markers of MD patients with and without migraine were compared by univariate analysis. Thereafter, binary Logistic regression was used to analyze the related factors of whether MD patients were accompanied with migraine. Results: Compared with the healthy control group, the peripheral blood WBC, neutrophils and FIB of MD patients were significantly increased (all P <0.05). Compared with MD patients without migraine, MD patients with migraine had higher female prevalence, longer disease history, lower low-frequency hearing threshold, higher frequency of vertigo attacks and higher HDL-C levels (all P <0.05), meanwhile, female, frequency of vestibular attacks and HDL-C were independent related factors of whether MD patients were accompanied with migraine. Conclusion: The occurrence of MD and migraine may be related to the inflammatory response. The level of anti-inflammatory factors in the blood of MD patients with migraine are higher, suggesting that the inflammatory response status of MD patients with and without migraine is different.

Using a Lewis acid-quenched CF 2 Ph - reagent, we show C-C bond formation through nucleophilic addition reactions to prepare molecules containing internal -CF 2 - linkages. We demonstrate C(sp 2 )-C(sp 3 ) coupling using both S N Ar reactions and Pd-catalysis. Finally, C(sp 3 )-C(sp 3 ) bonds are forged using operationally simple S N 2 reactions that tolerate medicinally-relevant motifs.

Dengue is one of the most prevalent infectious diseases in the world. Rapid, accurate and scalable diagnostics are key to patient management and epidemiological surveillance of the dengue virus (DENV), however current technologies do not match required clinical sensitivity and specificity or rely on large laboratory equipment. In this work, we report the translation of our smartphone-connected handheld Lab-on-Chip (LoC) platform for the quantitative detection of two dengue serotypes. At its core, the approach relies on the combination of Complementary Metal-Oxide-Semiconductor (CMOS) microchip technology to integrate an array of 78 × 56 potentiometric sensors, and a label-free reverse-transcriptase loop mediated isothermal amplification (RT-LAMP) assay. The platform communicates to a smartphone app which synchronises results in real time with a secure cloud server hosted by Amazon Web Services (AWS) for epidemiological surveillance. The assay on our LoC platform (RT-eLAMP) was shown to match performance on a gold-standard fluorescence-based real-time instrument (RT-qLAMP) with synthetic DENV-1 and DENV-2 RNA and extracted RNA from 9 DENV-2 clinical isolates, achieving quantitative detection in under 15 min. To validate the portability of the platform and the geo-tagging capabilities, we led our study in the laboratories at Imperial College London, UK, and Kaohsiung Medical Hospital, Taiwan. This approach carries high potential for application in low resource settings at the point of care (PoC)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moser, Yu, Rodriguez Manzano, Malpartida-Cardenas, Au, Arkell, Cicatiello, Moniri, Miglietta, Wang, Wang, Holmes, Chen and Georgiou.)

Taking the Jianghugongmi producing area as the research object, As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil of the study area were sampled and determined. The correlation of heavy metals was discussed using the multivariate statistical method, the spatial distribution interpolation analysis of heavy metals was carried out using ArcGIS 10.2, the quantitative source analysis of heavy metal pollution was carried out using the enrichment factor (EF) and PMF methods, and the potential ecological risk was evaluated. The results showed that the contents of the soil heavy metals As, Cd, Cu, Hg, Pb, and Zn were lower than the screening values specified in the standard for soil pollution risk control of agricultural land (GB 15618-2018), and the soil ecological environment risk was low; the maximum values of Cr and Ni exceeded the risk screening values, but the risk was low. The main distribution range of pH in the study area was 6.05-6.69, which was suitable for rice growth. The Mohe River indicated the spatial distribution of pH and heavy metals, which was closely related to the supergene geochemical characteristics of the elements. However, Hg and Cd showed different spatial distribution characteristics under human influence. Hg was distributed in the middle and high value distribution area along the west side of the river, and the spatial distribution of Cd was significantly different from north to south. The quantitative source analysis results based on the EF method and PMF showed that the main sources of heavy metals in the study area were agricultural sources, mixed sources, coal sources, and natural sources. The contribution rates of various sources accounted for 24.2%, 35.4%, 9.5%, and 30.9%, respectively. The medium strong ecological risk points of Hg in the study area were distributed along the west side of the Mohe River, whereas the moderate potential ecological risk points of Cd were concentrated in the cultivated land on both sides of the Mohe River, and the potential ecological risk index ( E r ) of the other elements was<40. Cd and Hg were the main potential ecological risk elements in the study area, whereas Cd was still the main potential pollution element in the cultivated land soil in the study area.

Background: Interleukin-8 (IL-8) and matrix metallopeptidase 9 (MMP9) are overexpressed in hepatocellular carcinoma (HCC), and both are related to tumor metastasis, but whether they regulate HCC metastasis is still unclear., Methods: HCC orthotopic implantation and colonization mice models were established in vivo . Model mice were treated with IL-8 and or MMP9 inhibitors, protein kinase C (PKC) inhibitors, or extracellular regulated protein kinases 1/2 (ERK1/2) inhibitors. Liver metastasis and lung metastasis of model mice were confirmed by hematoxylin and eosin staining. The population of circulating tumor cells (CTCs) was detected by flow cytometry. The expression of MMP9 in tumor tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro , HCC LM6 (HCCLM6) cells were treated with IL-8 combined PKC inhibitor or ERK1/2 inhibitor. The expression of MMP9 was confirmed by qRT-PCR and Western blot, and the activation of the PKC/ERK1/2 signaling pathway was confirmed by Western blot., Results: IL-8 promoted liver metastasis and lung metastasis in orthotopic transplantation model mice, increased the proportion of CTCs and promoted the expression of MMP9 in tumor tissues, but these effects were reversed by PKC inhibitor or ERK1/2 inhibitor. In vivo colonization experiments, IL-8 promoted tumor cell metastasis to the liver and lung, but the MMP9 inhibitor reversed the metastasis-promoting effect of IL-8. In cell experiments, IL-8 promoted the expression of p-PKC and p-ERK1/2 and inhibited the expression of PKC and ERK1/2; the promotion of MMP9 expression by IL-8 was reversed by PKC inhibitor or ERK1/2 inhibitor., Conclusions: IL-8 up-regulated the expression of MMP9 by activating the PKC/ERK1/2 signaling pathway, thereby promoting the metastasis and colonization of HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-37/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC ( p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC ( p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Objective: To review and analyze the cases of interventricular septal hematoma (IVSH) following surgical correction of the ventricular septal defect (VSD) in infants in our center., Methods: Retrospective analysis was performed on five infants with IVSH after surgical correction of VSD in our center from January 2020 to January 2022. The general preoperative information and intraoperative and postoperative results were collected and analyzed., Results: All five infants with VSD were repaired under cardiopulmonary bypass and occurred IVSH. The cardiac arrest occurred in one patient five hours after return to the intensive care unit (ICU). The patient's hemodynamics were difficult to maintain after cardiopulmonary resuscitation, and the patient died. Two other patients had arrhythmia and unstable hemodynamics during the perioperative period, the hematoma puncture was performed, and the patients' symptoms lessened. Perioperative and postoperative echocardiography showed that the hematoma gradually was shrunk, and the hemodynamics became stable. The hemodynamics were stable in the remaining two infants during the perioperative period. No specific medical intervention was required other than clinical observation in these two patients. Finally, the four infants successfully were discharged with good clinical results., Conclusion: IVSH is a rare complication of surgical repair of VSD. Prevention and early detection of IVSH during operation in infants with VSD are essential.

Pathological changes of the cochlea and hearing loss have been well addressed in Waardenburg syndrome (WS). However, the vestibular organ malformation in WS is still largely unknown. In this study, the differentiation and development of vestibular sensory epithelium and vestibular function caused by SOX10 mutation, a critical gene induces WS, have been studied in minature pig model. Degeneration of vestibular hair cells was found in this Sox10 mutation porcine model. Inner ear phenotype of the SOX10 +/R109W miniature pigs showed cochlear abnormalities as well as saccular hypofunction. In the mutant pigs, no prominent dissimilarity was shown in the bone structure of the semicircular canals. However, the saccular membrane was collapsed, and the infusion of stereocilia of the hair cells was observed. There were no dark cells in the utricles in the mutant pigs. The density of the utricular hair cells was also significantly lower in the mutant pigs compared to the wild type. Our study demonstrated that the SOX10 gene and melanocytes play important roles in the vestibular organ development. Sox10 mutation disrupts the KIT-DCT signaling pathway, affects the development of melanocytes, and leads to vestibule morphogenesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The optimal treatment strategy for patients with early glottic (T1-2N0M0) squamous cancer remains unclear., Methods: A retrospective population-based analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance treatment arms, and Cox regression analysis was used to determine prognostic factors for survival. Kaplan-Meier analysis, log-rank tests, and competing risk analysis were used to compare survival outcomes between treatment modalities (surgery vs. radiotherapy)., Results: Among the 3,994 eligible patients in this study, surgery was associated with improved cancer-specific survival (CSS) and overall survival (OS) compared with radiotherapy (log-rank test, P<0.05). This survival trend favoring surgery was consistent in the T1a, well/moderately differentiated grade, male, and all age subgroups. However, after the baseline characteristics were balanced with PSM, the survival outcomes (CSS and OS) did not differ significantly between the surgery and radiotherapy groups. Interestingly, surgery was associated with a 39% reduced risk of cancer-related death compared with radiotherapy in patients aged ≥70 years (hazard ratio 0.61; 95% CI: 0.43-0.87; P=0.006). However, this survival trend favoring surgery was not observed in younger patients (age <70 years), T stage subgroups, male or female subgroups, or in any of the pathological grade subgroups., Conclusions: In patients with early glottic squamous cell carcinoma undergoing surgery or radiotherapy, there is no sufficient evidence favoring one method over another in terms of survival. However, surgery is recommended in patients aged ≥70 years because, in this group, it was associated with improved survival outcomes compared with radiotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5288/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To investigate the safety and effectiveness of extraluminal placement of a bronchial blocker compared with carbon dioxide (CO 2 ) artificial pneumothorax in infants undergoing video-assisted thoracoscopic surgery (VATS)., Methods: The study involved 33 infants (group A) who underwent one-lung ventilation (OLV) with extraluminal placement of a bronchial blocker and 35 other infants (group B) who underwent CO 2 artificial pneumothorax. Clinical characteristics, the degree of lung collapse, and complications were compared., Results: The degree of lung collapse in group A was significantly higher than that in group B at T2 and T3. The mean arterial pressure (MAP) of group B was significantly lower than that of group A at 10 min and 30 min after OLV. The partial pressure of carbon dioxide (PaCO 2 ) of group B was significantly higher than that of group A at 30 min after OLV. The incidence of hypotension in group B was higher than that in group A., Conclusion: Compared with CO 2 artificial pneumothorax, extraluminal placement of a bronchial blocker is associated with a better degree of lung collapse, fewer episodes of hypotension, and lower PaCO 2 accumulation during OLV in infants undergoing VATS.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Xue, Shi, Xue, Zhang, Ma, Yu, Liu, Wang and Peng.)

Objective: The primary objective of this study was to assess the effect of selective lobar blockade on the risk of hypoxemia during one-lung ventilation in pediatric patients undergoing thoracoscopic surgery., Design: This was a retrospective matched case-control cohort study., Setting: The study was performed in a teaching hospital., Participants: A total of 60 pediatric patients who underwent thoracoscopic surgery in the authors' hospital from March 2020 to March 2021 were analyzed., Interventions: The authors examined their electronic medical records and found 30 patients in whom selective lobar blockade was used. These patients then were matched to 30 other patients in whom routine main bronchial blockade was performed in the authors' center based on age, weight, sex, side of surgery, and type of surgery., Measurements and Main Results: The inclusion criteria were four-fold: (1) pediatric patients with scheduled thoracoscopic resection of the middle and lower lobe lesions; (2) no obvious anesthesia or surgical contraindications; (3) American Society of Anesthesiologists class I to II; and (4) age younger than one year old. The exclusion criteria were as follows: (1) pediatric patients whose trachea was intubated with a size less than 3.0 mm; (2) a difficult airway; (3) changes in ventilation patterns during surgery; and (4) severe pneumonia and respiratory and circulatory system dysfunction. The following patient data were collected: (1) general clinical information; (2) mean arterial blood pressure, heart rate, central venous pressure, airway peak pressure (Ppeak), oxygenation index (PaO 2 /F I O 2 ratio), and alveolar-arterial oxygen differential pressure (AaDO2) at different time points; that is, before one-lung ventilation (OLV) (T1), ten minutes after OLV (T2), and ten minutes after the end of OLV (T3); (3) degree of lung collapse ten minutes after OLV; (4) operative duration; and (5) the prevalence of hypoxemia, the number of adjustments required for intraoperative displacement of the bronchial blocker, and pulmonary atelectasis. A total of 135 patients were selected, and 60 pediatric patients (30 in group S and 30 in group R) were included in this study. There were no significant differences in age, sex, weight, general preoperative data, degree of lung collapse, or operative duration (p > 0.05). The perioperative hemodynamics between the two groups were not statistically significant (p > 0.05). The oxygenation index, AaDO2, and Ppeak were not significantly different between the two groups at the T1 time point (p > 0.05). However, the oxygenation index was higher, and AaDO2 and Ppeak were lower in group S than in group R at the T2 and T3 time points (p < 0.05). The incidence of atelectasis, the prevalence of hypoxemia, and the number of adjustments required for intraoperative displacement of the bronchial blocker in group S were lower than those in group R (p < 0.05)., Conclusion: Selective lobar bronchial blockade, using a bronchial blocker in pediatric thoracoscopic surgery, may represent an alternative to excluding the main bronchial blockade for patients undergoing middle and lower lobe procedures, which may improve intraoperative oxygenation and reduce postoperative atelectasis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: African Swine Fever (ASF) is a highly contagious and lethal viral disease of swine, the presence of which in groups of pigs leads to enormous economic losses in the farming industry. However, vaccines and drugs to treat ASF have yet to be developed. To control the spread of the African Swine Fever Virus (ASFV), a diagnostic method that can be applied rapidly and can detect the disease during the early stages of infection is urgently needed., Methods: In this study, we demonstrate a rapid and easy-to-use ASFV detection method that combines loop-mediated isothermal amplification (LAMP) and image processing with the hue-saturation-value (HSV) color model. This method was validated through use of synthetic ASFV DNA., Results: The method shows high sensitivity, as it detects as few as 10 copies per reaction within 20 min. The speed and sensitivity of this newly developed assay are superior to those reported in previous studies. In addition, through HSV color space transformation, the colorimetric result of this LAMP assay can be used for a semi-quantitative analysis for ASFV (ranging from 10 8 to 10 1 copies per reaction) and improve the discern to low concentration samples from a negative control., Conclusion: These results show that the combination of ASFV-LAMP assay and HSV color space transformation may accelerate the screening process of pigs for ASFV infection. Overall, this study provides a rapid, sensitive, early-stage, on-site diagnosis of ASFV infection and has potential to be applied to other infectious diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Background: Few satisfactory animal models of laryngopharyngeal reflux (LPR) is available. Interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) may be associated with the pathogenesis of LPR injuries and laryngeal carcinomas., Objectives: To establish an animal model of LPR and to explore the related pathological changes and cytokine expression in the vocal cord tissue., Methods: Twenty rabbits were divided into experimental and control groups. Dilatation of the upper and lower esophageal sphincter were carried out in the experimental group. The pH of the pharynx, pathological, and ultrastructural changes of the laryngeal tissue, and expression of IL-8 and VEGF were compared between the experimental group and controls., Results: pH monitoring results and the dilated intercellular space of the vocal cord mucosa showed that the experimental group developed laryngopharyngeal reflux. There were significant differences in the immunohistochemical staining scores of both IL-8 (P = 0.015) and VEGF (P = 0.007) between the experimental and control groups in the vocal cord tissue., Conclusions: We successfully established a model of LPR, showing histopathological and ultrastructural changes consistent with the disease. The expression of IL-8 and VEGF may increase during the pathogenesis of LPR., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Pancreatic cancer is a leading cause of cancer death, and boron neutron capture therapy (BNCT) is one of the promising radiotherapy techniques for patients with pancreatic cancer. In this study, we evaluated the biological effectiveness of BNCT at multicellular levels using in vitro and in silico models. To recapture the phenotypic characteristic of pancreatic tumors, we developed a cell self-assembly approach with human pancreatic cancer cells Panc-1 and BxPC-3 cocultured with MRC-5 fibroblasts. On substrate with physiological stiffness, tumor cells self-assembled into 3D spheroids, and the cocultured fibroblasts further facilitated the assembly process, which recapture the influence of tumor stroma. Interestingly, after 1.2 MW neutron irradiation, lower survival rates and higher apoptosis (increasing by 4-fold for Panc-1 and 1.5-fold for BxPC-3) were observed in 3D spheroids, instead of in 2D monolayers. The unexpected low tolerance of 3D spheroids to BNCT highlights the unique characteristics of BNCT over conventional radiotherapy. The uptake of boron-containing compound boronophenylalanine (BPA) and the alteration of E-cadherin can partially contribute to the observed susceptibility. In addition to biological effects, the probability of induced α-particle exposure correlated to the multicellular organization was speculated to affect the cellular responses to BNCT. A Monte Carlo (MC) simulation was also established to further interpret the observed survival. Intracellular boron distribution in the multicellular structure and related treatment resistance were reconstructed in silico. Simulation results demonstrated that the physical architecture is one of the essential factors for biological effectiveness in BNCT, which supports our in vitro findings. In summary, we developed in vitro and in silico self-assembly 3D models to evaluate the effectiveness of BNCT on pancreatic tumors. Considering the easy-access of this 3D cell-assembly platform, this study may not only contribute to the current understanding of BNCT but is also expected to be applied to evaluate the BNCT efficacy for individualized treatment plans in the future.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms., (© 2021. The Author(s).)

Objective: To observe the gadolinium imaging findings of inner ear in patients with sudden deafness and to analyze its clinical features. Methods: From November 2017 to July 2020, 21 patients with sudden deafness in the People's Hospital of Dongsheng District, Ordos City were selected as the research objects, including 14 males and 7 females, aged 36-76 years, with a median age of 50 years. The course of disease was 1-19 days, with an average of 5.5 days. The patients received audiology tests, laboratory examination, and intravenous gadolinium angiography, each of whom was scanned twice by 3D-FLAIR sequence: once before intravenous gadolinium injection, and once again 4.5-6.0 h after intravenous gadolinium injection. The following corresponding clinical treatment was given. The imaging manifestations and clinical features were observed. Results: Among 21 cases of sudden deafness in acute stage, the signal intensity of 11 cases was significantly higher than that of the contralateral ear, and 2 cases had vestibular labyrinthine hydrops. In laboratory examination, only 2 cases of total deafness had increased WBC count and faster erythrocyte sedimentation rate, and the rest had no abnormality. The hearing types of 21 patients with sudden deafness were: total deafness in 8 cases, flat decline in 10 cases, low frequency decline in 1 case, high frequency decline in 2 cases. The total effective rate was 57% (12/21). The hearing types of 11 patients with abnormal gadolinium angiography were total deafness in 5 cases, flat decline in 5 cases and high frequency decline in 1 case. The total effective rate was 64% (7/11). Conclusion: Gadolinium angiography is abnormal in some patients with sudden deafness, and the permeability of blood labyrinth barrier may be increased, which is worthy of further study.

Background: To evaluate the safety and effectiveness of remifentanil-based fast-track cardiac anesthesia (FTCA) combined with the postoperative serratus anterior plane block (SAPB) for transthoracic device closure of atrial septal defect (ASD) in pediatric patients., Methods: A total of 70 children who underwent transthoracic device closure of ASDs from January 2018 to June 2020 were divided into two groups according to different anesthesia strategies administered, namely group F (fast-track anesthesia, n = 38) and group R (routine anesthesia, n = 32), and relevant clinical data were collected and analyzed., Results: There was no statistically significant difference between the two groups in general preoperative data, intraoperative hemodynamics, and FLACC score 1 h after extubation (p > .05). FLACC score of Group F was significantly lower than that of group R at 4, 8, 12, and 24 h after extubation (p < .05). The number of postoperative PCA press and the dose of PCA infusion in group F were lower than those in group R (p < .05). The mechanical ventilation duration, the length of intensive care unit stay in group F were statistically significantly lower than those in group R (p < .05)., Conclusion: Remifentanil-based FTCA combined with the postoperative SAPB for transthoracic device closure of ASD in pediatric patients could effectively reduce postoperative pain of the children., (© 2021 Wiley Periodicals LLC.)

The olfactory system is used by insects to find hosts, mates, and oviposition sites. Insects have different types of olfactory proteins, including odorant-binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs), and sensory neuron membrane proteins (SNMPs) to perceive chemical cues from the environment. The greater wax moth, Galleria mellonella , is an important lepidopteran pest of apiculture. However, the molecular mechanism underlying odorant perception in this species is unclear. In this study, we performed transcriptome sequencing of G. mellonella antennae to identify genes involved in olfaction. A total of 42,544 unigenes were obtained by assembling the transcriptome. Functional classification of these unigenes was determined by searching against the Gene Ontology (GO), eukaryotic orthologous groups (KOG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. We identified a total of 102 olfactory-related genes: 21 OBP s, 18 CSP s, 43 OR s, 18 IR s, and 2 SNMP s. Results from BLASTX best hit and phylogenetic analyses showed that most of the genes had a close relationship with orthologs from other Lepidoptera species. A large number of OBP s and CSP s were tandemly arrayed in the genomic scaffolds and formed gene clusters. Reverse transcription-quantitative PCR results showed that GmelOBP19 and GmelOR47 are mainly expressed in male antennae. This work provides a transcriptome resource for olfactory genes in G. mellonella , and the findings pave the way for studying the function of these genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Liu, Jiang, Wang, Xiao, Gao, Sheng, Shi, Zeng, Yu and Cao.)