Is a brief mindfulness ecological momentary intervention more efficacious than a self-monitoring app for social anxiety disorder? A randomized controlled trial.

Despite their proliferation, limited knowledge exists regarding possible benefits of brief mindfulness ecological momentary interventions (MEMIs) for social anxiety disorder (SAD). Propositions that MEMIs could alleviate SAD symptoms and related clinical outcomes remain untested. This trial evaluated a 14-day MEMI for SAD. Participants with self-reported SAD were randomized to MEMI (n = 96) or self-monitoring app (SM; n = 95). Whereas MEMI instructed mindfulness exercises, SM prompted only self-monitoring five times daily for 14 days. Participants completed state-level self-reports of depression, anxiety, and mindfulness pre-post-mindfulness practice and SAD symptoms, worry, depression severity, repetitive negative thinking, and trait mindfulness at pre-randomization, post-intervention, and 1-month follow-up (1MFU). Hierarchical linear modeling was conducted. The MEMI yielded statistically significantly larger improvements in momentary depression, anxiety, and mindfulness (Cohen's d = -0.10-0.11). Although no between-group effects emerged in alleviating SAD fear and avoidance, excessive worry, depression severity, repetitive negative thinking, and trait mindfulness (-0.13-0.15), within-group effects were significantly small-to-large from pre-post and pre-1MFU (-4.62-0.67). A significant reduction in depression severity occurred in MEMI (-0.63--0.60) but not SM (-0.31--0.29). Brief MEMI and SM yielded nondifferent sustained effects on SAD, comorbid symptoms, and risk factors, highlighting its potential value within stepped-care delivery settings.

Testing the Efficacy of a Brief, Self-Guided Mindfulness Ecological Momentary Intervention on Emotion Regulation and Self-Compassion in Social Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: Theories propose that brief, mobile, self-guided mindfulness ecological momentary interventions (MEMIs) could enhance emotion regulation (ER) and self-compassion. Such changes are posited to be mechanisms of change. However, rigorous tests of these theories have not been conducted. OBJECTIVE: In this assessor-blinded, parallel-group randomized controlled trial, we aimed to test these theories in social anxiety disorder (SAD). METHODS: Participants with SAD (defined as having a prerandomization cut-off score ≥20 on the Social Phobia Inventory self-report) were randomized to a 14-day fully self-guided MEMI (96/191, 50.3%) or self-monitoring app (95/191, 49.7%) arm. They completed web-based self-reports of 6 clinical outcome measures at prerandomization, 15-day postintervention (administered the day after the intervention ended), and 1-month follow-up time points. ER and self-compassion were assessed at preintervention and 7-day midintervention time points. Multilevel modeling determined the efficacy of MEMI on ER and self-compassion domains from pretrial to midintervention time points. Bootstrapped parallel multilevel mediation analysis examined the mediating role of pretrial to midintervention ER and self-compassion domains on the efficacy of MEMI on 6 clinical outcomes. RESULTS: Participants demonstrated strong compliance, with 78% (149/191) engaging in at least 80% of the MEMI and self-monitoring prompts. MEMI was more efficacious than the self-monitoring app in decreasing ER goal-directed behavior difficulties (between-group Cohen d=-0.24) and lack of emotional clarity (Cohen d=0.16) and increasing self-compassion social connectedness (Cohen d=0.19), nonidentification with emotions (Cohen d=0.16), and self-kindness (Cohen d=0.19) from pretrial to midintervention time points. The within-group effect sizes from pretrial to midintervention were larger in the MEMI arm than in the self-monitoring app arm (ER goal-directed behavior difficulties: Cohen d=-0.73 vs -0.29, lack of emotional clarity: Cohen d=-0.39 vs -0.21, self-compassion domains of social connectedness: Cohen d=0.45 vs 0.19, nonidentification with emotions: Cohen d=0.63 vs 0.48, and self-kindness: Cohen d=0.36 vs 0.10). Self-monitoring, but not MEMI, alleviated ER emotional awareness issues (between-group Cohen d=0.11 and within-group: Cohen d=-0.29 vs -0.13) and reduced self-compassion acknowledging shared human struggles (between-group Cohen d=0.26 and within-group: Cohen d=-0.23 vs 0.13). No ER and self-compassion domains were mediators of the effect of MEMI on SAD symptoms (P=.07-<.99), generalized anxiety symptoms (P=.16-.98), depression severity (P=.20-.94), repetitive negative thinking (P=.12-.96), and trait mindfulness (P=.18-.99) from pretrial to postintervention time points. Similar nonsignificant mediation effects emerged for all of these clinical outcomes from pretrial to 1-month follow-up time points (P=.11-.98). CONCLUSIONS: Brief, fully self-guided, mobile MEMIs efficaciously increased specific self-compassion domains and decreased ER difficulties associated with goal pursuit and clarity of emotions from pretrial to midintervention time points. Higher-intensity MEMIs may be required to pinpoint the specific change mechanisms in ER and self-compassion domains of SAD. TRIAL REGISTRATION: Open Science Framework (OSF) Registries; osf.io/m3kxz https://osf.io/m3kxz.

Photosensitized covalent organic framework as a light-induced oxidase mimic for colorimetric detection of uric acid.

As large numbers of people are suffering from gout, an accurate, rapid, and sensitive method for the detection of gout biomarker, uric acid, is important for its effective control, diagnosis, and therapy. Although colorimetric detection methods based on uricase have been considered, they still have limitations as they produce toxic H2O2 and are expensive and not stable. Here, a novel uricase-free colorimetric method was developed for the sensitive and selective detection of uric acid based on the light-induced oxidase-mimicking activity of a new photosensitized covalent organic framework (COF) (2,4,6-trimethylpyridine-3,5-dicarbonitrile-4-[2-(4-formylphenyl)ethynyl]benzaldehyde COF [DCTP-EDA COF]). DCTP-EDA COF has a strong ability to harvest visible light, and it could catalyze the oxidation of 1,4-dioxane, 3,3',5,5'-tetramethylbenzidine under visible light irradiation to produce obvious color changes. With the addition of uric acid, however, the significant inhibition of the oxidase-mimicking activity of DCTP-EDA COF remarkably faded the color, and thus uric acid could be colorimetrically detected in the range of 2.0-150 µM with a limit of detection of 0.62 µM (3σ/K). Moreover, the present colorimetric method exhibited high selectivity; uric acid level in serum samples was successfully determined, and the recoveries ranged from 96.5% to 105.64%, suggesting the high accuracy of the present colorimetric method, which demonstrates great promise in clinical analysis.

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer.

BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. CONCLUSIONS: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. CLINICAL TRIAL REGISTR ATION: Clinicaltrials.gov (NCT03475251).

Construction of covalent organic framework nanozymes with photo-enhanced hydrolase activities for colorimetric sensing of organophosphorus nerve agents.

Construction of covalent organic frameworks (COFs)-based nanozymes is of great importance for the extensive applications in catalysis and sensing fields. In this work, a two-dimensional COF (DAFB-DCTP COF) was fabricated via Knoevenagel condensation reaction. The integration of catalytically active sites of pyridine groups into the donor-acceptor (D-A) conjugated skeleton endows DAFB-DCTP COF with both hydrolytic and photosensitive properties. The DAFB-DCTP COF can be utilized as an artificial enzyme with selective and photo-enhanced catalytic efficiency, facilitating its application in photocatalytic degradation of hydrolase substrates (p-nitrophenyl acetate, pNPA) by nucleophilic reaction and further realizing colorimetric detection of the nanozyme inhibitor of organophosphorus nerve agent (diethyl cyanophosphonate, DCNP). The distinct color changes could be distinguished by naked eyes even at a low DCNP concentration, and the versatile smartphone analysis featured with reliability and simplicity. For the first time, the COFs' intrinsic hydrolase activity depending on their structural characteristics was investigated in synergy with the photosensitive performance originating from their photoelectric features. The present contribution provides a promising direction towards construction of colorimetric sensing platform based on the regulation of COFs' non-oxidoreductase activity under visible light irradiation.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Economic and cost-effectiveness aspects of vaccines in combating antibiotic resistance.

Antimicrobial resistance (AMR) is a global public health threat causing substantial morbidity and mortality as well as significant economic costs. Vaccines can contribute to combating antimicrobial resistance by reducing the incidence of resistant disease cases and lowering overall antibiotic use. Greater utilization and investments in vaccines as a tool for combating AMR might be hampered by limited economic evidence demonstrating the AMR-related value of vaccines. We reviewed the existing literature to assess the state of evidence. We found two modeling studies that provided estimates of AMR-related costs averted by pneumococcal vaccination and a few cost-effectiveness studies that exclusively focused on serotype replacement effects on overall vaccine cost-effectiveness. We did not find any cost-effectiveness studies that directly examined the cost-effectiveness of vaccines in slowing the development of AMR. Further evidence on the cost-effectiveness and economic value of vaccines in controlling AMR can help inform resource allocation decisions and guide development priorities.

Hydroxysafflor Yellow A Exerts Neuroprotective Effect by Reducing Aß Toxicity Through Inhibiting Endoplasmic Reticulum Stress in Oxygen-Glucose Deprivation/Reperfusion Cell Model.

Ischemia stroke is thought to be one of the vascular risks associated with neurodegenerative diseases, such as Alzheimer's disease (AD). Hydroxysafflor yellow A (HSYA) has been reported to protect against stroke and AD, while the underlying mechanism remains unclear. In this study, SH-SY5Y cell model treated with oxygen-glucose deprivation/reperfusion (OGD/R) was used to explore the potential mechanism of HSYA. Results from cell counting kit-8 (CCK-8) showed that 10 µM HSYA restored the cell viability after OGD 2 hours/R 24 hours. HSYA reduced the levels of malondialdehyde and reactive oxygen species, while improved the levels of superoxide dismutase and glutathione peroxidase. Furthermore, apoptosis was inhibited, and the expression of brain-derived neurotrophic factor was improved after HSYA treatment. In addition, the expression levels of amyloid-ß peptides (Aß) and BACE1 were decreased by HSYA, as well as the expression levels of binding immunoglobulin heavy chain protein, PKR-like endoplasmic reticulum (ER) kinase pathway, and activating transcription factor 6 pathway, whereas the expression level of protein disulfide isomerase was increased. Based on these results, HSYA might reduce Aß toxicity after OGD/R by interfering with apoptosis, oxidation, and neurotrophic factors, as well as relieving ER stress.

Tanshinone IIA ameliorates Aß transendothelial transportation through SIRT1-mediated endoplasmic reticulum stress.

BACKGROUND: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD. METHODS: Aß1-42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aß deposition respectively. RESULTS: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both animals and cells. CONCLUSION: Tan IIA could promote Aß transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice.

HBV genotype-dependent association of HLA variants with the serodecline of HBsAg in chronic hepatitis B patients.

Seroclearance of hepatitis B surface antigen (HBsAg) is regarded as the functional cure for chronic hepatitis B (CHB). The relationship between human leukocyte antigen (HLA) variants, hepatitis B virus genotype, and longitudinal HBsAg serodecline remains to be explored. A total of 1735 HBeAg-seronegative CHB patients with genotype B or C infection of the community-based REVEAL-HBV cohort were genotyped for rs1710 (HLA-G) and rs2770 (HLA-B) using TaqMan assay. Cox proportional hazard regression and generalized linear mixed models were used to analyze the association of HLA genetic variants with the rate of HBsAg seroclearance and longitudinal HBsAg serodecline. Rs1710 G allele was differentially associated with the HBsAg seroclearance in genotype B [aRR (95% CI) = 0.74 (0.56-0.98)] and genotype C [aRR (95%CI) = 1.43 (1.08-1.88)] infection. Rs2770 G allele was associated with HBsAg seroclearance only in genotype B infection [aRR (95% CI) = 0.69 (0.52-0.91)]. The alleles associated with HBsAg seroclearance were significant predictors for the serodecline of HBsAg levels in an HBV genotype-dependent manner (genotype B infection: rs1710, P = 0.013; rs2770, P = 0.0081; genotype C infection: rs1710, P = 0.0452). Our results suggest both spontaneous HBsAg seroclearance and serodecline are modified by the interaction between HLA variants and HBV genotype.

Simultaneous detection and separation of uranium based on a fluorescent amidoxime-functionalized covalent organic polymer.

To ensure the long-term sustainable development of nuclear energy as well as the prevention and control of uranium pollution, new materials that can simultaneously detect and separate uranium are still urgently needed. Herein, a new fluorescent covalent organic polymer (COP), namely HT-COP-AO, was synthesized andemployed as both the fluorescent probe and absorbent for simultaneous uranium detection and separationconsidering its excellent fluorescence property and strong uranium coordination ability. The results showed that the fluorescence of HT-COP-AO was quickly quenched by uranium within 2 min, and the limit of detection was 0.23 µM (3σ/K). Further studies implied that uranium was coordinated with the amidoxime groups of HT-COP-AO through U-N and O = U = O bonds, which resulted in electron transfer from uranium to HT-COP-AO and quenching the fluorescence of HT-COP-AO consequently. Meanwhile, HT-COP-AO exhibited excellent absorption ability towards uranium, and the maximum absorption capacity (qmax = 401.3 mg/g) was higher than most reported amidoxime modified materials. The HT-COP-AO also showed high selectivity for both uranium detection and separation which makes it a great promising for uranium monitoring in real water samples.

The association of air pollutants with hospital outpatient visits for child and adolescence psychiatry in Shenzhen, China.

BACKGROUND: Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. METHODS: A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO2, PM2.5, SO2 and O3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. RESULT: A total of 94,660 cases aged 3-18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M0) showed that in the single lag effect result, when the average daily concentration of NO2 at 24 µg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO2 M0 value to the outpatient visits were 1.438 (1.137-1.818) over lag 0-2, 1.454 (1.120-1.887) over lag 0-3, 1.466 (1.084-1.982) over lag 0-4, 1.680 (1.199-2.354) over lag 0-5, 1.993 (1.369-2.903) over lag 0-6, and 2.069 (1.372-3.119) over lag 0-7. However, PM2.5, SO2, O3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO2 increases by 10 units or when the maximum concentration of NO2 is reached. CONCLUSION: Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP.

Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV.

BACKGROUND & AIMS: Hepatitis B core-related antigen (HBcrAg) is a surrogate seromarker of intrahepatic hepatitis B virus covalently closed circular DNA quantity and activity and a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B patients. We assess association between HBcrAg and HCC in individuals seronegative for hepatitis B surface antigen and anti-hepatitis C virus (NBNC) in Taiwan. METHODS: A total of 129 newly developed HCC cases and 520 frequency-matched non-HCC controls were drawn from the REVEAL-NBNC cohort. Serum HBcrAg and other risk factors measured at recruitment were compared between cases and controls. Regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The proportion of baseline HBcrAg positivity (≥1000 U/mL) was significantly higher in HCC cases than in controls (12.4% vs 1.4%, P < .001). In multivariate analysis, HBcrAg positivity was associated with significantly higher risk of HCC (adjusted OR [95% CI]: 9.3 [3.3-26.4]; P < .001]. The HCC population attributable to HBcrAg positivity was 11.1% (95% CI: 9.7%-12.5%). CONCLUSIONS: Seropositivity of HBcrAg might identify a subset of the NBNC population at higher risk of HCC in hepatitis B virus endemic areas.

Increased risk of olfactory and taste dysfunction in the United States psoriasis population.

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.

Relationship Between Expression of microRNA and Chemotherapy Resistance in Cervical Carcinoma.

Cervical cancer (CC), although being a potentially avoidable disease, is the second most often diagnose gynecological cancer, with at minimum 530,000 new instant reported each year, and optimism for CC remains poor. Nearly half of individuals with locally advanced cervical cancer have a poor pathological response to standard therapy. As a result, research into the molecular pathogenesis of cervical cancer and associated therapeutic targets is a must. MicroRNAs (miRNAs) are possible biomarkers in cervical cancer; elevations or reductions in many distinct miRNAs discovered in individuals with this illness indicate that miRNA could contain a function to play in the illness's pathogenesis. Nevertheless, little is known about their significance in detecting individuals who do not respond to traditional therapy. As a consequence, the intention of this study is to look at the relationship among the synthesis of miRNAs (miR 217 and miR-140-3p), which can be utilized as molecular biomarkers to predict pathological responses in cervical cancer patients after radiation and chemotherapy. Various analytical techniques were used to analyze the data, including quantitative real-time PCR (qRT-PCR), growth and apoptosis analysis, western blot analysis, luciferase reporter gene analysis, immunohistochemistry, and statistical analysis. The results show that such miRNAs participate a crucial responsibility in CC cell proliferation inhibition. They might be a new therapeutic target for microRNA-mediated cell proliferation inhibition in cervical cancer.

Clinical diagnosis and treatment of multiple pulmonary nodules / 中华肿瘤杂志

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.

Effect of Gandouling Decoction Combined with Cognitive Behavioral Therapy on Impulse Control Disorders in Wilson's Disease with Syndrome of Combined Phlegm and Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with cognitive behavioral therapy （CBT） in the treatment of impulse control disorders in patients with Wilson's disease （WD， syndrome of combined phlegm and stasis）. MethodA prospective study was conducted on 90 WD patients with the syndrome of combined phlegm and stasis and impulse control disorders （ICD） treated in the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from August 2018 to February 2023. They were randomized into a control group， a CBT group， and a treatment group， with 30 patients in each group. The control group received routine Western medicine treatment （basic copper removal）. The CBT group received cognitive behavioral therapy in addition to the therapy in the control group， and the treatment group received Gandouling decoction in addition to the therapy in the CBT group. Each course of treatment was 8 days， and the patients were treated for 4 courses. Before and after treatment， the 24-hour urine copper （24 h U-Cu）， non-ceruloplasmin-bound copper （NCC）， traditional Chinese medicine （TCM） syndrome score， unified WD rating scale part Ⅲ （UWDRS Ⅲ） score， Barratt Impulse Scale Version 11 （BIS-11） score， Buss-Perry aggression questionnaire （BPAQ） score， modified overt aggression scale （MOAS） score， and treatment emergent symptom scale （TESS） score of three groups of patients were determined and statistically analyzed. ResultBefore treatment， there was no statistically significant difference in the level of 24 h U-Cu or NCC among the three groups. After treatment， all the three groups showed an increase in 24 h U-Cu （P<0.01） and a decrease in the NCC level （P<0.05， P<0.01）. There was no significant difference in the 24 h U-Cu level among the three groups after treatment. After treatment， the NCC level showed no significant difference between the control group and the CBT group， while the NCC level in the treatment group was lower than that in the control group and CBT group （P<0.05）. Before treatment， there was no statistically significant difference in the TCM syndrome score among the three groups. After treatment， the TCM syndrome scores of all the three groups decreased （P<0.01）. Moreover， the treatment group had lower TCM syndrome score than the control group and CBT group （P<0.05）. Before treatment， the UWDRS Ⅲ， BIS-11， BPAQ， and MOAS scores had no statistically significant differences among the three groups. After treatment， the UWDRS Ⅲ， BIS-11， BPAQ， and MOAS in all the three groups declined （P<0.05）. Moreover， the CBT group and treatment group had lower UWDRS Ⅲ， BIS-11， BPAQ， and MOAS scores than the control group （P<0.05）， and the treatment group had lower BIS-11 and BPAQ scores than the CBT group （P<0.05）. ConclusionThe combination of Gandouling decoction and CBT can ameliorate impulse control disorders in the WD patients with combined phlegm and stasis.

The efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma / 中华泌尿外科杂志

Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.

Study on the consistency between thoracic electrical bioimpedance and pulse index continuous cardiac output in hemodynamic monitoring of elderly patients with septic shock / 中华老年医学杂志

Objective:The hemodynamic parameters of elderly patients with septic shock were measured simultaneously with pulse index continuous cardiac output(PiCCO)and thoracic electrical bioimpedance(TEB)to evaluate the accuracy of TEB and to provide empirical evidence for its clinical use.Methods:A total of 24 elderly patients with septic shock admitted to the intensive care unit of our hospital between July 2021 and December 2021 were retrospectively recruited.TEB and PiCCO hemodynamic monitoring were performed continuously in all patients, and hemodynamic data were collected for statistical analysis.Results:Cardiac output, cardiac index, stroke volume, stroke index and systemic vascular resistance measured by the two methods had no significant difference( P>0.05). The 95% confidence intervals in the Bland-Altman plots for cardiac output, CI, stroke volume, stroke index, and systemic vascular resistance were(-1.18, 1.25), (-0.65, 0.71), (-24.23, 37.00), (-12.93, 19.26)and(397.11, 425.83). In the Bland-Altman plots for cardiac output, cardiac index, stroke volume and systemic vascular resistance, 4.17% of the points(1/24)fell outside of the 95% confidence interval, and in the Bland-Altman plots for stroke index, 8.33% of the points(2/24)fell outside of the 95% confidence interval. Conclusions:TEB and PiCCO have good consistency in evaluating the hemodynamics of elderly patients with septic shock.Therefore, TEB can be recommended for community hospitals and used in elderly patients.

The relationship among pubertal timing, overweight and obesity and eating disorders in adolescents / 中国学校卫生

Objective@#To understand the relationship among pubertal timing, overweight and obesity, and eating disorders among Bengbu adolescents, and to provide a reference for obesity prevention.@*Methods@#Two nine year schools were conveniently selected in Bengbu, with 683 students from grade 5 to grade 8. Puberty Development Scale (PDS) and Eating Disorders Inventory of Children (EDI-C) subscale were used, height and weight were measured. The associations between obesity, pubertal timing and eating disorders were analyzed.@*Results@#The prevalence of overweight and obesity was higher in boys than that in girls, and the rate of early pubertal timing, drive for thinness score, body dissatisfaction score and total eating disorder score were higher in girls than that in boys( χ 2/t =28.69, 57.99, 3.47, 2.59, 3.30, P <0.05). The differences in rate of overweight and obesity, bulimia score and total eating disorder score were statistically significant by grade( χ 2/F =28.39, 5.11, 3.95, P ＜0.01). There was a positive correlation among overweight obesity and early pubertal timing and eating disorder, and a positive correlation between early pubertal timing and eating disorder( r =0.18, 0.17, 0.14, P < 0.01 ). The mediating effect of early pubertal timing between overweiht, obesity and eating disorders partially contributed 14.25% to the total effect.@*Conclusion@#Overweight and obesity is associated with eating disorders, and early pubertal timing partially mediate the association between overweight obesity and eating disorders. Healthy lifestyle should be advocated in family and school to effectively prevent adolescents obesity, pubertal timing, and eating disorders.