Efficacy and inflammatory levels (IL-6, IL-10) of adjuvant application of vitamin-A in the treatment of pediatric Mycoplasma pneumoniae pneumonia: a systematic review and meta-analysis.

Objective: The purpose of this study is to evaluate the efficacy of Vitamin A (VitA) as an adjuvant therapy for pediatric Mycoplasma Pneumoniae Pneumonia (MPP) through meta-analysis, and to investigate its impact on inflammation levels (IL-6, IL-10), in order to explore the role of VitA in pediatric MPP. Methods: Using a systematic literature search method, relevant research literature is searched, and RCT studies that meet the requirements are selected based on preset inclusion and exclusion criteria. Then, a quality evaluation was conducted on the included literature, and meta-analysis was used to calculate the combined effect values of mortality rate, hospital stay, lung rale disappearance time, cough duration, fever duration, IL-6 and IL-10 levels, and heterogeneity analysis was conducted. The levels of IL-6 and IL-10 represent the inflammatory levels in pediatric MPP patients, and exploring their changes has significant implications for the anti-inflammatory effect of treatment. Results: A total of 10 RCT studies were included, with a total sample size of 1,485, including 750 cases in the control group and 735 cases in the observation group. The meta-analysis results of this study showed that there was a significant difference in the total clinical efficacy of using VitA adjuvant therapy compared to the control group without VitA [OR = 3.07, 95%CI = (2.81, 4.27)], P < 0.05. However, there was no significant difference in the adverse reaction rate between the use of VitA as an adjuvant therapy and the control without VitA [OR = 1.17, 95%CI = (0.61, 2.27)], P > 0.05. At the same time, the hospitalization time [MSD = -0.86, 95% CI = (-1.61, -0.21)], lung rale disappearance time [MSD = -0.78, 95%CI = (-1.19,-0.51)], cough duration [MSD = -1.07, 95%CI = (-1.41, -0.71)], and fever duration [MSD = -0.47, 95%CI = (-0.72, -0.23)] using VitA as an adjuvant treatment were obviously lower. In addition, the meta-analysis outcomes also showed that the use of VitA adjuvant therapy can significantly reduce IL-6 [MSD = -1.07, 95%CI = (-1.81, -0.27)] and IL-10 [MSD = -0.13, 95%CI = (-0.31, 0.12)] levels. This indicates that the application of VitA in pediatric MPP also has the effect of reducing inflammatory response. Conclusion: Based on the meta-analysis results, VitA adjuvant therapy can significantly improve the clinical symptoms of pediatric MPP patients, shorten hospitalization time, promote the disappearance of lung rales, and alleviate cough and fever symptoms. In addition, VitA adjuvant therapy can effectively reduce inflammation levels, indicating its potential role in inhibiting inflammatory responses. In clinical practice, VitA adjuvant therapy for pediatric MPP can be promoted as a potential treatment option.

Are routine, daily chest radiographs (CXR) necessary following (VATS and RATS) lobectomies?

Background: Consensus guidelines regarding the amount and necessity of post-operative imaging in thoracic surgery are lacking. The efficacy of daily chest radiographs (CXR) following video-assisted (VATS) and robotic-assisted (RATS) thoracoscopic surgery in directing management has not been previously studied. We hypothesize that abnormal clinical findings, rather than abnormal imaging findings, better predict post-operative complications in patients undergoing VATS/RATS lobectomies. Methods: A retrospective review of VATS and RATS lobectomy patients were performed at a tertiary referral center from 1/1/2019-12/31/2021. Demographics, hospital course, and imaging were evaluated. Descriptive statistics, Chi-Square test, Fisher's exact, Wilcoxon rank sum, and multivariable logistic regression were performed. Our outcomes were post-operative complications requiring a procedure and extended length of stay (LOS) (>2 days post-operatively). Results: Out of 362 VATS/RATS lobectomy patients, 15 patients had post-operative complications requiring a procedure. Almost all patients who required a procedure had abnormal clinical signs and symptoms (14/15; p < 0.001) while 70 % had expected post-operative day (POD) one CXR findings (11/15; p = 0.463). Multivariable logistic regression demonstrated clinical signs and symptoms independently predicted procedural requirement (odds ratio [OR] = 48, 95 % Confidence Interval [CI]:8.5-267) while abnormal POD one imaging did not. For extended LOS, a positive smoking history (OR = 4.4, 95 % CI:1.4-14.1), number of CXRs (OR = 2.4, 95 % CI:1.8-3.2) and thoracostomy tubes (OR = 5.3, 95 % CI:1.0-27.3) were independent predictors while clinical signs and symptoms was not. Conclusion: Abnormal clinical findings may guide management more predictably than abnormal CXRs after VATS/RATS. Routine CXR in the post-operative setting may be unnecessary in those without clinical signs or symptoms. Key message: There are no consensus guidelines regarding the efficacy of routine, post-operative diagnostic studies after major thoracic lobar resections. The presence of abnormal signs or symptoms after minimally invasive lobectomies may better predict those who will require additional procedures better than the presence of abnormal routine, post-operative chest radiographs.

Using scalable computer vision to automate high-throughput semiconductor characterization.

High-throughput materials synthesis methods, crucial for discovering novel functional materials, face a bottleneck in property characterization. These high-throughput synthesis tools produce 104 samples per hour using ink-based deposition while most characterization methods are either slow (conventional rates of 101 samples per hour) or rigid (e.g., designed for standard thin films), resulting in a bottleneck. To address this, we propose automated characterization (autocharacterization) tools that leverage adaptive computer vision for an 85x faster throughput compared to non-automated workflows. Our tools include a generalizable composition mapping tool and two scalable autocharacterization algorithms that: (1) autonomously compute the band gaps of 200 compositions in 6 minutes, and (2) autonomously compute the environmental stability of 200 compositions in 20 minutes, achieving 98.5% and 96.9% accuracy, respectively, when benchmarked against domain expert manual evaluation. These tools, demonstrated on the formamidinium (FA) and methylammonium (MA) mixed-cation perovskite system FA1-xMAxPbI3, 0 ≤ x ≤ 1, significantly accelerate the characterization process, synchronizing it closer to the rate of high-throughput synthesis.

Risk of Gastric and Small Intestinal Cancer in Patients With Lynch syndrome - Data From a Large, Community-Based U.S. Population.

INTRODUCTION: Risk of gastric and small intestinal cancer in Lynch syndrome (LS) remains poorly understood. We investigated the risk of gastric and small intestinal cancer in patients with LS in a large, community-based population. METHODS: This retrospective cohort study included all patients diagnosed with LS between 1/1/1997-12/31/2020 at Kaiser Permanente Northern California. Cumulative incidence of gastric cancer and small intestinal cancer was calculated using competing risk methodology. RESULTS: Among 1106 LS patients with a median follow-up of 19.3 years (interquartile range [IQR] 9.4-24.0 years), 11 developed gastric cancer (8 MSH2, 2 MLH1 and 1 PMS2) with the median diagnosis age of 56 years (IQR 42-63 years); 11 developed small intestinal cancer (6 MSH2, 3 MLH1, 1 MSH6 and 1 PMS2) with the median diagnosis age of 57 years (IQR 50-66 years). Cumulative incidence by age 80 years was 7.26% (95% confidence internal [CI], 1.80-18.03%) for men and 3.43% (95% CI, 0.50-11.71%) for women for gastric cancer, and was 7.28% (95% CI, 3.19-13.63%) for men and 2.21% (95% CI, 0.23-9.19%) for women for small intestinal cancer. Pathogenic variants (PV) carriers of MSH2 and MLH1 had the highest risk of gastric and small intestinal cancer. History of Helicobacter pylori (H. pylori) infection was associated with increased risk of gastric cancer (adjusted odds ratio 5.52; 95% CI, 1.72-17.75). DISCUSSION: Patients with LS, particularly MSH2 and MLH1 PV carriers, had significantly increased lifetime risk of gastric and small intestinal cancer. Testing and treatment of H. pylori should be considered for all patients with LS.

[Mechanism of ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix regulates HIF-1α signaling pathway mediated by renal hypoxia to ameliorate renal fibrosis in DKD rats].

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.

Growing attention on the toxicity of Chinese herbal medicine: a bibliometric analysis from 2013 to 2022.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM's toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade. Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations. Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019-2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology. Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

Corrigendum: Comparison of cardiac function between single left ventricle and tricuspid atresia: assessment using echocardiography combined with computational fluid dynamics.

[This corrects the article DOI: 10.3389/fped.2023.1159342.].

Ultrasonic optic nerve sheath diameter can be used as a diagnostic measure after accidental dural puncture during cesarean section: a case report.

BACKGROUND: Parturients are prone to postdural puncture headache (PDPH) after epidural puncture. Cerebral venous sinus thrombosis (CVST) is a fatal complication of PDPH. The main symptom of both is headache, however, the mechanism is not similar. For persistent PDPH, early differential diagnosis from CVST is essential. Optic nerve sheath diameter (ONSD) measurements can be used to identify changes in intracranial pressure as an auxiliary tool to distinguish the cause of headache. CASE PRESENTATION: The dura of a 32-year-old woman undergoing cesarean section was accidentally penetrated while administering epidural anesthesia, and the patient developed PDPH the subsequent day. The patient refused epidural blood patch (EBP) treatment and was discharged after conservative treatment. Fourteen days post-discharge, she was readmitted for a seizure. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) indicated low cranial pressure syndrome and superior sagittal sinus thrombosis with acute infarction. The next morning, the EBP was performed with 15 ml autologous blood. Subsequently, the headache symptoms decreased during the day and worsened at night. ONSD measurement suggested dilation of the optic nerve sheath, and subsequently, the patient showed intracranial hypertension with papilledema. After dehydration and anticoagulant treatment, the patient's symptoms were relieved and she was discharged from the hospital 49 days later. CONCLUSIONS: Headache is the main symptom of PDPH and cerebral venous thrombosis, which are difficult to distinguish. ONSD measurement may help to estimate the intracranial pressure, and early measurement may be helpful for women with PDPH to avoid serious complications, such as CVST.

STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

Mid-term Incidence of Tarsometatarsal Joint Arthrodesis Following Open Reduction With Internal Fixation (ORIF) of Lisfranc Injuries.

Open reduction with internal fixation (ORIF) of Lisfranc injuries are associated with an increased risk for secondary surgery including hardware removal and salvage arthrodesis. In the current literature, rates of salvage arthrodesis vary due to small sample sizes and a low incidence of Lisfranc injuries. There is little evidence to identify specific surgical and patient-related variables that may result in later arthrodesis. The purpose of this study is to determine the rate of tarsometatarsal joint arthrodesis following Lisfranc ORIF in a relatively large sample size. This retrospective review included patients who underwent ORIF for a Lisfranc injury between January 2007 and December 2012. A total of 146 patients met our criteria. Trans-articular fixation was used in 109 (74.6%) patients, 33 (22.6%) received percutaneous fixation and 4 (2.7%) extraarticular fixation. Five out of 120 (4.2%) patients required a salvage arthrodesis for post-traumatic arthritis that had a follow-up greater than 5 y but up to 10 y. The mean age of patients who underwent arthrodesis after ORIF was 24.5 ± 11.95 (16-48) y compared to 40.9 ± 15.8 (16-85) y. Patients who required an arthrodesis also had earlier hardware removal than patients who did not have an arthrodesis, 71.2 ± 28.3 (38-100) days and 131.4 ±101.2 (37-606) days, respectively. Patients who required salvage arthrodesis tended to be younger and hardware was removed earlier compared to those patients who did not require an arthrodesis. Four of the 5 patients who underwent a secondary arthrodesis had a loss of correction after hardware removal.

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.

Introduction: Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary. Methods: This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes. Discussion: To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

CEP55-associated lethal fetal syndrome: a case report of a Chinese family.

Background: Research on fetal loss related to germline mutations in single genes remains limited. Disruption of CEP55 has recently been established in association with perinatal deaths characterized by hydranencephaly, renal dysplasia, oligohydramnios, and characteristic dysmorphisms. We herein present a Chinese family with recurrent fetal losses due to compound heterozygous nonsense CEP55 variants. Case presentations: The Chinese couple had a history of five pregnancies, with four of them proceeding abnormally. Two stillbirths (II:3 and II:4) sequentially occurred in the third and fourth pregnancy. Prenatal ultrasound scans revealed phenotypic similarities between fetuses II:3 and II:4, including oligohydramnios, bilateral renal dysplasia and hydrocephalus/hydranencephaly. Clubfoot and syndactyly were also present in both stillborn babies. Fetus II:3 presented with endocardial cushion defects while fetus II:4 did not. With the product of conception in the fourth pregnancy, whole exome sequencing (WES) on fetus II:4 identified compound heterozygous nonsense CEP55 variants comprised of c.190C>T(p.Arg64*) and c.208A>T(p.Lys70*). Both variants were expected to result in lack of the TSG101 and ALIX binding domain. Sanger sequencing confirmed the presence and cosegregation of both variants. Conclusion: This is the fifth reported family wherein biallelic CEP55 variants lead to multiple perinatal deaths. Our findings, taken together with previously described phenotypically similar cases and even those with a milder and viable phenotype, broaden the genotypic and phenotypic spectrum of CEP55-associated lethal fetal syndrome, highlighting the vital biomolecular function of CEP55.

Inequalities in the Incidence of Psychotic Disorders Among Racial and Ethnic Groups.

OBJECTIVE: The authors examined recent trends in incidence of psychotic disorders, demographic characteristics, and comorbid psychiatric and medical conditions among six racial/ethnic groups. METHOD: A retrospective cohort study design was used to examine the incidence of psychotic disorders across race/ethnicity groups and comorbid psychiatric and medical conditions among members of Kaiser Permanente Northern California from 2009 to 2019 (N=5,994,758). Poisson regression was used to assess changes in annual incidence, and Cox proportional hazards and logistic regression models adjusted for age and sex were used to test correlates and consequences. RESULTS: Overall, the incidence of nonaffective psychotic disorders decreased slightly over the study period. Compared with White members, the risk of nonaffective psychosis diagnosis was higher among Black (hazard ratio=2.13, 95% CI=2.02-2.24) and American Indian or Alaskan Native (AIAN) (hazard ratio=1.85, 95% CI=1.53-2.23) members and lower among Asian (hazard ratio=0.72, 95% CI=0.68-0.76) and Hispanic (hazard ratio=0.91, 95% CI=0.87-0.96) members, as well as those whose race/ethnicity was categorized as "other" (hazard ratio=0.92, 95% CI=0.86-0.99). Compared with White members, the risk of affective psychosis diagnosis adjusted for age and sex was higher among Black (hazard ratio=1.76, 95% CI=1.62-1.91), Hispanic (hazard ratio=1.09, 95% CI=1.02-1.16), and AIAN (hazard ratio=1.38, 95% CI=1.00-1.90) members and lower among Asian (hazard ratio=0.77, 95% CI=0.71-0.83), Native Hawaiian or other Pacific Islander (hazard ratio=0.69, 95% CI=0.48-0.99), and "other" (hazard ratio=0.86, 95% CI=0.77-0.96) members. Psychotic disorders were associated with significantly higher odds of suicide (odds ratio=2.65, 95% CI=2.15-3.28), premature death (odds ratio=1.30, 95% CI=1.22-1.39), and stroke (odds ratio=1.64, 95% CI=1.55-1.72) and lower odds of health care utilization (odds ratio=0.44, 95% CI=0.42-0.47). CONCLUSIONS: This study demonstrates racial and ethnic variation in incident psychotic disorder diagnoses in the United States, compared with non-Hispanic Whites. Individuals diagnosed with psychosis face a greater burden of other negative health outcomes and lower odds of health care utilization, reflecting personal and economic impacts. Identifying risk factors for elevated rates and protective influences in subgroups can inform strategies for prevention and interventions to ameliorate severe consequences of psychotic syndromes.

[Chemical Oxygen Demand(COD) Composition and Contribution in Typical Waters of Baiyangdian Lake].

Chemical oxygen demand (COD) is an important index used to assess organic oxygen consumption pollution. To explore COD composition in the natural water in Baiyangdian Lake, the main composition, source, and influencing factors of oxygen-consuming organic substances in the water body were revealed through physical continuous classification, three-dimensional fluorescence, and other methods. The results showed that the COD of the two waters was affected by dissolved organic substances (protein-like and humus-like organic matters) with size of less than 220 nm (59%-93%), and inorganic substances had little effect on COD. The source of organic matter in overlying water was primarily affected by endophytic vegetation decomposition, sediment release (the release flux of TOC was in the range of 1.55-2.28 mg·(m2·d)-1), and other endogenous sources (biological index>0.8), as well as by land-based sources such as reed platform and artificial pollution (1.4

Comparative Study on Tuberculosis Drug Resistance and Molecular Detection Methods Among Different Mycobacterium Tuberculosis Lineages.

Purpose: This study aims to compare drug resistance and detection efficacy across different Mycobacterium tuberculosis lineages, offering insights for precise treatment and molecular diagnosis. Methods: 161 strains of Mycobacterium tuberculosis (M.tb) were tested for drug resistance using Phenotypic Drug Susceptibility Testing (pDST), High-Resolution Melting analysis (HRM), and Whole Genome Sequencing (WGS) methods. The main focus was on evaluating the accuracy of different methods for detecting resistance to rifampicin (RIF), isoniazid (INH), and streptomycin (SM). Results: Among the 161 strains of M.tb, 83.85% (135/161) were fully sensitive to RIF, INH, and SM according to pDST, and the rate of multidrug resistance was 4.35% (7/161). The drug resistance rates of lineage 2 M.tb to the three drugs (26/219, 11.87%) were significantly higher than those of non-lineage 2 M.tb (12/264, 4.45%) (P<0.05). Compared with pDST, WGS had a sensitivity of 100%, 94.12%, and 92.31% and a specificity of 100%, 99.31%, and 98.65% for RIF, INH, and SM, respectively, with no significant difference. The sensitivity of HRM for RIF, INH, and SM was 87.50%, 52.94%, and 76.92%, respectively, while the specificity was 96.08%, 99.31%, and 99.32%, respectively. The sensitivity of HRM for detecting INH resistance was significantly lower than that of pDST (P=0.039). Compared with HRM, WGS increased the sensitivity of RIF, INH, and SM by 12.50%, 41.18%, and 15.38%, respectively. Conclusion: There are significant differences in drug resistance rates among different lineages of M.tb, with lineage 2 having higher rates of RIF, INH, and SM resistance than lineages 3 and 4. The sensitivity of HRM is far lower than that of pDST, and currently, the accuracy of HRM is not sufficient to replace pDST. WGS has no significant difference in detecting drug resistance compared with pDST but can identify new anti-tuberculosis drug-resistant mutations, providing effective guidance for clinical decision-making.

[Characterization of genetic variants in children with refractory epilepsy].

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION: 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

Germline Genetic Testing Among Women ≤ 45 Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System.

BACKGROUND: We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. METHODS: A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. RESULTS: A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. CONCLUSION: In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Discovering the processes of undergraduate hospitality students' acceptance of facebook teaching interventions.

Technology drives innovation and reform in hospitality education, and Facebook has become a popular educational tool to facilitate students' classroom interactions. Understanding hospitality students' attitudes toward Facebook teaching interventions is important. Based on a survey of 289 undergraduate hospitality students, first, we expand the scope of the technology acceptance model (TAM) in this study, which integrates the two factors of social interaction and information exchange into the research structure. Second, this study also proposes a new moderated mediation model to account for the internal mechanism underlying Taiwanese undergraduate hospitality students' acceptance of Facebook teaching interventions in terms of perceived usefulness and ease of use. We illuminate the foundation of the application of Facebook media technology to teaching in hospitality higher education. The theoretical contributions and educational implications of this research are also discussed.

Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol.

Introduction: Rebound pain, transient and acute postoperative pain after the disappearance of regional block anesthesia, has been a concern in recent years. Insufficient preemptive analgesia and hyperalgesia induced by regional block are the main mechanisms. At present, the evidence for the treatment of rebound pain is limited. The esketamine, as an antagonist of the N-methyl-D-aspartate receptor, has been proven to prevent hyperalgesia. Therefore, this trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Methods/design: This study is a single-center, prospective, double-blind, randomized, placebo-controlled trial. Participants who plan to undergo total knee arthroplasty will be randomly assigned to the esketamine group (N = 178) and placebo group (N = 178) in a ratio of 1:1. This trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. The primary outcome of this trial is the incidence of rebound pain within 12 h after the operation in the esketamine group and the placebo group. The secondary outcome will be to compare (1) the incidence of rebound pain 24 h after the operation; (2) the time to enter the pain cycle for the first time within 24 h after the procedure; (3) the first time of rebound pain occurred within 24 h after surgery; (4) the modified rebound pain score; (5) NRS score under rest and exercise at different time points; (6) the cumulative opioid consumption at different time points; (7) patient's prognosis and knee joint function evaluation; (8) blood glucose and cortisol concentration; (9) patient's satisfaction score; (10) adverse reactions and adverse events. Discussion: The effect of ketamine on preventing postoperative rebound pain is contradictory and uncertain. The affinity of esketamine to the N-methyl-D-aspartate receptor is about four times higher than levo-ketamine, the analgesic effect is 3 times higher than levo-ketamine, and there are fewer adverse mental reactions. To our knowledge, there is no randomized controlled trial to verify the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Therefore, this trial is expected to fill an important gap in relevant fields and provide novel evidence for individualized pain management. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300069044.