Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q₁, Q₃)] of 0.40 (0.22-0.8) ng·g^-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q₁, Q₃)] of 0.13 (0.09, 0.17) ng·g^-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant^-1·day^-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q₁, Q₃)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q₁, Q₃)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
Humans ; Beijing ; Wastewater-Based Epidemiological Monitoring ; Sewage/analysis* ; Wastewater ; Ketamine/analysis* ; Codeine/analysis* ; Methadone/analysis* ; Water Pollutants, Chemical/analysis*

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.
Humans ; Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Molecular Docking Simulation ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Capsules ; Atherosclerosis ; Cerebral Infarction ; Neoplasms

Objective: To compare and analyze the effect of repairing small skin and soft tissue defect wounds in functional areas of children with full-thickness skin grafts from different sites of abdomen. Methods: A prospective randomized controlled study was conducted. From January 2019 to June 2020, 60 female children with small skin and soft tissue defects in functional areas requiring full-thickness skin grafting, who met the inclusion criteria, were admitted to the First Affiliated Hospital of Air Force Medical University. According to the random number table, the children were divided into two groups, with 28 cases left in lateral abdomen group aged 5 (3, 8) years and 29 cases in lower abdomen group aged 5 (3, 7) years after the exclusion of several dropped-out children in follow-up. In lower abdomen group, 20 (12, 26) cm² wounds of children were repaired with (24±10) cm² full-thickness skin graft from transverse skin lines in the inferior abdomen area, while in lateral abdomen group, 23 (16, 32) cm² wounds of children were repaired with (24±9) cm² full-thickness skin graft from below the umbilical plane to above the groin in the lateral abdomen area. All the children were treated with continuous intradermal suture at the donor site incision and received continuous negative pressure treatment of -10.64 to -6.65 kPa in the donor and recipient areas after operation. The donor site was treated with a medical skin tension-reducing closure device since post-surgery day (PSD) 7. The use of medical skin tension-reducing closure device at the donor site, postoperative complications and suture removal time of the donor area were recorded, and the incidence of complications was calculated. On PSD 7, a self-designed efficacy satisfaction questionnaire was used to investigate the parents' satisfaction with the curative effect of their children. In post-surgery month (PSM) 1 and 6, Vancouver scar scale (VSS) was used to evaluate the scar at the donor site, and the VSS score difference between the two time points was calculated; the scar width at the donor site was measured with a ruler, and the scar width difference between the two time points was calculated. Data were statistically analyzed with independent sample t test or Cochran & Cox approximate t test, Mann-Whitney U test, and Fisher's exact probability test. Results: The proportion of children in lateral abdomen group who used the medical skin tension-reducing closure device in the donor area for equal to or more than 4 weeks after surgery was significantly higher than that in lower abdomen group (P<0.05). On PSD 7, there was one case of partial incision dehiscence in the donor area, one case of peripheral skin redness and swelling in the donor area, and one case of fat liquefaction in the donor area in lateral abdomen group, and one case of partial incision dehiscence in the donor area in lower abdomen group. The incidence of postoperative complications at the donor site of children in lower abdomen group was significantly lower than that in lateral abdomen group (P<0.05). Compared with that in lateral abdomen group, the suture removal time at the donor site of children after surgery in lower abdomen group was significantly shorter (t'=17.23, P<0.01). On PSD 7, the satisfaction score of parents with the curative effect of their children in lower abdomen group was significantly higher than that in lateral abdomen group (t'=20.14, P<0.01). In PSM 1 and 6, the VSS scores of scar at the donor site of children in lower abdomen group were 2.7±0.9 and 2.8±1.0, respectively, which were significantly lower than 7.1±2.2 and 9.1±2.7 in lateral abdomen group (with t values of 10.00 and 11.15, respectively, P<0.01). In PSM 6, the VSS score of scar at the donor site of children in lateral abdomen group was significantly higher than that in PSM 1 (t=3.10, P<0.01), while the VSS score of scar at the donor site of children in lower abdomen group was not significantly higher than that in PSM 1 (P>0.05). The VSS score difference of scar at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-8.12, P<0.01). In PSM 1 and 6, the scar widths at the donor site of children in lower abdomen group were 2.0 (1.0, 2.0) and 2.0 (2.0, 3.0) mm, respectively, which were significantly narrower than 6.0 (4.0, 10.0) and 8.5 (5.0, 12.0) mm in lateral abdomen group (with Z values of -13.41 and -14.70, respectively, P<0.01). In PSM 6, the scar width at the donor site of children in lateral abdomen group was significantly wider than that in PSM 1 (Z=-2.79, P<0.01), while the scar width at the donor site of children in lower abdomen group was not significantly wider than that in PSM 1 (P>0.05). The difference of scar width at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-14.93, P<0.01). Conclusions: The use of full-thickness skin grafts from the lower abdomen to repair small skin and soft tissue defect wounds in functional areas of children, especially girls, is effective, simple and easy to operate, and conforms to the principle of aesthetic repair. Compared with transplantation with full-thickness skin graft from the lateral abdomen, lower abdominal full-thickness skin grafting has a low incidence of donor site complications and no obvious scar hyperplasia, which is worthy of clinical promotion.
Abdominal Cavity/surgery* ; Child ; Cicatrix/surgery* ; Female ; Humans ; Postoperative Complications/surgery* ; Prospective Studies ; Skin Transplantation ; Wound Healing

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Objective: Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM Methods: EVs were isolated from the serum of healthy subjects, quantified Results: PM Conclusions EVs treatment promotes cell survival and attenuates PM
A549 Cells ; Air Pollutants/toxicity* ; Apoptosis/drug effects* ; Cell Survival/drug effects* ; Extracellular Vesicles ; Humans ; Male ; Middle Aged ; Particulate Matter/toxicity* ; Protective Agents/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Serum

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.
Diagnosis ; Epidemiology* ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Methods ; Nasopharyngeal Neoplasms ; Prognosis ; Proportional Hazards Models ; SEER Program ; Survival Rate

PURPOSE: The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. RESULTS: Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. CONCLUSION: Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.
Chemoradiotherapy ; Disease-Free Survival ; Humans ; Induction Chemotherapy* ; Lymphocytes ; Neutropenia* ; Neutrophils ; Prognosis

Objective To explore the role of signal transducer and activator of transcription 3 (STAT3) phosphorylation in the pathogenesis of Behcet's disease (BD),and to investigate the association between STAT3 phosphorylation and disease activity in BD patients.Methods Peripheral blood mononuclear cell (PBMC) was isolated from 15 mL peripheral boood of 10 active BD patients (BD-A),10 BD patients in remission (BD-R) and 10 healthy controls (HC) respectively.The blockade of STAT3 phosphorylation was performed by Stattic.The PBMC was divided into Stattic subgroup (treated with 2.5 μmol/L stattic and 1 640 medium,5 mL) and blank control subgroup (treated with 5 mL 1 640 medium),respectively.The protein levels of phosphorylated STAT3 (pSTAT3) and STAT3 were examined by flow cytometry and Western blot.The protein and mRNA levels of TNF-α,IFN-γ and IL-17 were tested by RT-PCR and ELISA.Two-way ANOVA and Bonferroni post hoc test were used to analyze the results.Results Compared with HC,the BD patients showed higher protein levels of pSTAT3 and STAT3,and higher protein and mRNA levels of TNF-α,IFN-γ and IL-17;compared with blank control subgroup,the protein levels of pSTAT3 and STAT3,and protein and mRNA levels of TNF-α,IFN-γ and IL-17 decreased in Stattic subgroup.In the BD-A group,the protein level of pSTAT3,and protein and mRNA levels of TNF-α,IFN-γ and IL-17 were significantly higher than those in the BD-R group.Conclusions An increased activation of the STAT3 pathway may contribute to the pathogenesis of BD and relate to disease activity in BD patients by inducing TH1 and Th17 cells activation.

Objective To evaluate the long-term efficacy of percutaneous pulmonary valve implantation (PPVI) and the durability of the home-made self-expanding pulmonary valve (Venus-P).Methods From May,2013 to Nov.,2015,14 patients who underwent percutaneous pulmonary valve implantation at Zhongshan Hospital,Fudan University and received at least 1 year follow-up were enrolled,including 3 males and 11 females,with an average age of (35.8 ± 7.8) years.All patients with tetralogy of Fallot received radical resection and developed severe pulmonary regurgitation.The longterm mortality,the operation related complications,the short term and long-term effect of PPVI,as well as the durability and effect of the self-expanding pulmonary valve were evaluated in the 14 patients.Results Over an average follow-up period of (2.3 ± 0.8) years (1.0-3.5 years),only 1 patient died (6.7 ％).During the follow-up,no deterioration,infective endocarditis,malignant arrhythmia and other serious complications was observed,and nobody needed reoperation.There was no valve displacement,valve stent fracture,obvious circumferential leakage and pulmonary regurgitation.After PPVI,an acute improvement in pulmonary artery diastolic pressure was observed [(4.93 ± 3.37) mmHg vs.(11.47 ± 4.61) mmHg,P＜0.05].Six month postoperatively,right ventricular end diastolic volume measured by cardiac nuclear magnetic resonance was significantly reduced [(139.29± 18.21)mL/m2 vs.(83.03 ± 20.0) mL/m2,P＜0.05].At 1 year follow up,the across valve pressure difference were (20.85 ± 4.45) mmHg calculated by the echocardiography,and the NYHA cardiac function (Ⅰ-Ⅲ:4 cases;Ⅰ-Ⅱ:10 cases) was improved 1-2 degree and the distance of 6-minute walk test were significantly increased [(475.00 ± 55.06) m vs.(594.23 ± 194.51) m,P＜0.05].Meanwhile,the QRS duration decreased was also observed.The changes of the QRS duration have statistical significance after 1 and 3 months of the PPVI when compared with the baseline [(169.93 ± 21.34) ms vs.(159.87 ± 24.4) ms or (160.00 ± 27.0 ms,P＜0.05].Conclusions PPVI using home-made self-expanding pulmonary valve (Venus-P) for chronic pulmonary regurgitation has good long-term efficacy and low complication rate,and the valve is durable.