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Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).Results: Of the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P

Tianmei Si,1 Kerang Zhang,2 Jisheng Tang,3 Maosheng Fang,4 Keqing Li,5 Jianmin Zhuo,6 Yu Feng6 1Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Beijing, People’s Republic of China; 2Shanxi Medical University First Hospital, Shanxi, People’s Republic of China; 3Mental Health Center of Shandong Province, Shandong, People’s Republic of China; 4Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People’s Republic of China; 5Mental Health Center of Hebei Province, Hebei, People’s Republic of China; 6Janssen Research and Development, Beijing, People’s Republic of China Abstract: This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75–150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions–Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: –30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short-term, placebo-controlled studies of paliperidone palmitate conducted in similar populations. Keywords: antipsychotic, long-acting injectable, PANSS

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC 50 values were determined to be 147.45 ± 6.05 μM, 11.86 ± 0.32 μM, and 10.50 ± 3.74 μM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 μM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/β-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

As an adaptor protein functions essentially in the activation of NF-κΒ and MAPK signaling pathways mediated by NOD1 and NOD2, RIP2 plays important roles in the host innate immune responses. In the present study, the RIP2 ortholog termed Lc-RIP2 was identified and characterized in large yellow croaker (Larimichthys crocea). It was revealed that Lc-RIP2 is consisted of an open reading frame (ORF) of 1695 bp, encoding a protein of 564 aa, with an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD). Subcellular localization assays demonstrated that Lc-RIP2 was a cytosolic protein, which was broadly distributed in the examined tissues/organs, and could be induced in response to poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulations in vivo according to qRT-PCR analysis. Notably, Lc-RIP2 overexpression in vitro was sufficient to abolish SVCV proliferation in EPC cells, and could significantly induce the activation of NF-κB, IRF3, IRF7, and IFN1 promoters. In addition, luciferase assays found that Lc-RIP2 could cooperate with Lc-MAVS, Lc-TRAF3, Lc-TRAF6, Lc-IRF3, and Lc-IRF7 in NF-κB activation, associate with Lc-TRIF, Lc-MAVS, Lc-TRAF3, Lc-IRF3, and Lc-IRF7 in IRF3 activation, enhance Lc-TRIF, Lc-MAVS, Lc-TRAF3, and Lc-TRAF6 mediated IRF7 activation, and Lc-IRF3 mediated IFN1 activation, whereas suppress NF-κB activation when co-expressed with Lc-TRIF. Co-immunoprecipitation (Co-IP) assays also demonstrated that Lc-RIP2 interacts separately with Lc-TRIF, Lc-MAVS, Lc-TRAF3, Lc-TRAF6, Lc-IRF3, and Lc-IRF7. It is thus collectively indicated that Lc-RIP2 function dominantly in the regulation of the host innate immune signaling., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction., Objective: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale., Methods: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment., Discussion: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo . As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1 , a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro -cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

Objective: The protein interacting with C kinase 1 (PICK1) plays a critical role in vesicle trafficking, and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome, which eventually disrupts acrosome formation and leads to male infertility., Methods: An azoospermia sample was filtered, and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient. We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene, c.364delA (p.Lys122SerfsX8), and this protein structure truncating variant seriously affected the biological function. Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology (CRISPRc)., Results: The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities, as well as dysfunctional mitochondrial sheath formation. Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice. Moreover, the mitochondrial dysfunction was verified in the mice. These defects in the male PICK1 knockout mice may have eventually led to complete infertility., Conclusion: The c.364delA novel variant in the PICK1 gene associated with clinical infertility, and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans., (© 2023. Huazhong University of Science and Technology.)

High activity nitrogen and sulfur co-doping high specific surface-modified peanut shell carbon PBC-NS was prepared through one-step carbonization using thiourea and phosphoric acid as modifiers. The TC/Cu(Ⅱ) adsorption characteristics of peanut shell carbon in single and mixed-adsorption systems were discussed, and the enhancement effect and mechanism of modification on TC/Cu(Ⅱ) adsorption were studied. The results showed that the modified peanut shell carbon PBC-NS successfully introduced nitrogen-sulfur functional groups such as Pyridinic N, Graphitic N, C- S-C, and -SH, and the modified specific surface area was as high as 1437 m 2 ·g -1 , which was 2.6 times higher than that before modification. The maximum adsorption capacities of modified peanut shell carbon PBC-NS for single-system TC and Cu(Ⅱ) were 585 mg·g -1 and 21.2 mg·g -1 , respectively, which were 2.6 times and 2.7 times higher than those before modification. The saturated adsorption capacities of TC and Cu(Ⅱ) in the system were increased by 13 mg·g -1 and 6.8 mg·g -1 compared with that in the single system. The adsorption capacity of PBC-NS for TC and Cu(Ⅱ) could still reach 66% and 70% of the initial adsorption capacity after four times of repeated use. Isotherm fitting and modern spectroscopic analysis indicated that the substantial increase in the adsorption capacity of TC/Cu(Ⅱ) on PBC-NS by modification was mainly attributed to the combined effect of chemical chelation of nitrogen-sulfur active functional sites and pore filling caused by high specific surface area. These results indicated that thiourea/phosphoric acid chemical modification could effectively improve the adsorption capacity of peanut shell carbon for TC/Cu(Ⅱ), which can provide a new idea for the structural regulation of mixed-pollution biochar with high adsorption capacity and adsorption treatment of TC/Cu(Ⅱ) water pollution.

Using cotton stalk as biomass raw material and phosphoric acid as a modifier, narrow pore distribution phosphorus-containing cotton stalk biochar (CSP) with a high surface area (1916 m 2 ·g -1 ) and pore volume (1.3982 mL·g -1 ) was prepared through one-step carbonization, and the adsorption characteristics and mechanisms for tetracycline (TC) were investigated. The results showed that the TC adsorption capacity of CSP was up to 669 mg·g -1 , which was 43.6 times that of unmodified cotton stalk carbon. FTIR, XPS, and isothermal adsorption studies showed that the high adsorption capacity of CSP for TC resulted from the joint action of complexation, hydrogen bonding, pore filling, and π-π dispersion forces, and the highly active phosphate ester group (P-O-C) endowed by phosphoric acid modification greatly enhanced the chemical interaction with TC molecules, which was the key factor for the significant increase in adsorption capacity. Isotherm and thermodynamic study further confirmed that chemical adsorption played a major role in the adsorption process, the adsorption process was spontaneous and endothermic, and the material had good regeneration performance. This study provides theoretical guidance for the preparation of modified biomass carbon with high adsorption performance to remove tetracycline antibiotic pollution.

The widespread testing for severe acute respiratory syndrome coronavirus 2 infection has facilitated the use of test-negative designs (TNDs) for modeling coronavirus disease 2019 (COVID-19) vaccination and outcomes. Despite the comprehensive literature on TND, the use of TND in COVID-19 studies is relatively new and calls for robust design and analysis to adapt to a rapidly changing and dynamically evolving pandemic and to account for changes in testing and reporting practices. In this commentary, we aim to draw the attention of researchers to COVID-specific challenges in using TND as we are analyzing data amassed over more than two years of the pandemic. We first review when and why TND works and general challenges in TND studies presented in the literature. We then discuss COVID-specific challenges which have not received adequate acknowledgment but may add to the risk of invalid conclusions in TND studies of COVID-19., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As a TIR domain-containing molecular, sterile α-and armadillo motif-containing protein (SARM) acts as an adaptor in Toll-like receptor (TLR) signaling, and also plays important roles in mediating apoptosis and neuronal injury. In the present study, the ortholog of SARM , named as Lc-SARM , was cloned and identified in large yellow croaker ( Larimichthys crocea ). The full-length ORF of Lc-SARM consists of 2,154 bp, encoding a protein of 717 amino acids (aa), which is comprised of an N-terminal ARM domain, two SAM domains, and a C-terminal TIR domain. Confocal microscopy revealed that Lc -SARM was mainly distributed in the cytoplasm, and the mRNA expression level of Lc-SARM was broadly distributed in all the detected organs/tissues, with the highest expression level found in the brain. The expression patterns of Lc-SARM could be induced in response to poly I:C, LPS, PGN stimulations, and Pseudomonas plecoglossicida infection. Notably, although the overexpression of Lc -SARM could significantly induce NF-κB, IRF3, IRF7, and type I IFN promoter activation, whereas the co-expression of Lc- SARM with Lc- TRIF, Lc -TRAF3, Lc -IRF3, or Lc -IRF7 significantly down-regulated the induction of NF-κB, IRF3, IRF7, or type I IFN promoter activation, and suppressed the antiviral effects as well as the downstream antiviral-related genes expression compared to the only overexpression of Lc -TRIF, Lc -TRAF3, Lc -IRF3, or Lc -IRF7. Co-immunoprecipitation (Co-IP) assays also demonstrated that Lc- SARM interacts separately with Lc -TRIF, Lc -TRAF3, Lc -IRF3, and Lc -IRF7. It is thus collectively suggested that Lc -SARM functions as a negative regulator in Lc -TRIF, Lc -TRAF3, and Lc -IRF3/7 involved antiviral signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Li, Tang, Li, Shen, Liu, Jiang, Zhang, Wang and Zou.)

Preliminary evidence indicates that natural disasters are associated with an increased risk for schizophrenia. With few longitudinal studies on earthquakes, this retrospective cohort study examined exposure to the 1976 Tangshan earthquake and the subsequent risk of schizophrenia. Population counts and visits to all nine psychiatric hospitals in Tangshan city were collected. We created three cohort groups by earthquake exposure: infant (August 1972 to July 1976 births), fetal (August 1976 to May 1977 births), and unexposed (June 1977 to May 1981 births). The cumulative incidence of schizophrenia in each cohort was calculated by dividing the number of schizophrenia patients by total births in the corresponding period. Altogether, 6424 schizophrenia patients were identified, with 2786 in the infant group, 663 in the fetal group, and 2975 in the unexposed group. The crude cumulative incidence of schizophrenia in the infant, fetal and unexposed groups were 7.64 (95% confidence interval [CI] = 7.36-7.92), 9.07 (95% CI = 8.38-9.76), and 7.40 (95% CI = 7.13-7.66) per thousand population respectively. Adjusted for mortality, the corresponding figures were 7.73 (95% CI = 7.44-8.01), 9.30 (95% CI = 8.60-10.01) and 7.44 (95% CI = 7.18-7.71) per thousand population respectively. The mortality-adjusted risk ratio (aRR) was 1.25 (95% CI = 1.15-1.36) between fetal and unexposed groups (χ 2  = 27.31, P < 0.001). Males exposed as infants did not differ from the unexposed in cumulative schizophrenia incidence. People with fetal exposure to the 1976 earthquake had 25% higher risk of developing schizophrenia compared to unexposed counterparts., (© 2022. The Author(s).)

Objective: Liver fibrosis is a frequently occurring liver injury which lacks of effective treatment clinically. Here, we investigated the protective effects of a novel compound Gorse isoflavone alkaloid (GIA) against liver fibrosis., Methods: Totally forty rats were randomly divided into four groups. Then we established a model of liver fibrosis induced by the intragastric administration of carbon tetrachloride (CCl 4 ). This treated group was followed by the intragastric administration of GIA and colchicine. Then the liver index and spleen index, and liver function indexes were detected by kit. Western blotting assay was performed to estimate the expression of Transforming Growth Factor-β1 (TGF-β1) and related proteins. Tissue fibrosis was observed by Masson staining., Results: Our results suggested that GIA reduced the deposition of collagen fibres and the fibrosis index hydroxyproline (Hyp) of liver tissue. Furthermore, we found that GIA significantly decreased the expression of Transforming Growth Factor-β1 (TGF-β1) and the ratio of p-smad2/3 to smad2/3, enhanced the level of superoxide dismutase (SOD), and decreased the concentration of malonic dialdehyde (MDA) in the liver., Conclusions: Our findings revealed that GIA has a beneficial effect to resist the liver fibrosis, and could be ideal for potential use in antifibrotic drugs for the liver., Competing Interests: None., (AJTR Copyright © 2022.)

A new species, Cylindroeme yunnanensis sp. nov., is described and illustrated from Yunnan Province of China. Cylindroeme vietnamica Vives, 2019 is recorded from China for the first time. A key to the species of Cylindroeme is provided.

Polymeric materials implanted in the human body are usually invisible under X-ray, and the mixing of heavy metal salts into polymeric materials by physical compounding often poses compatibility problems. A new iodine-containing cyclic carbonate monomer, 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide (IBTMC), is synthesized, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the side chain in the form of covalent bonds. The ring-opening polymerization of IBTMC is achieved at room temperature under the catalysis of the solid superbase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). The structure and X-ray developing ability of the synthesized polycarbonate are characterized by 1 H-NMR, X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), Gel Permeation Chromatography (GPC), and micro-computed tomography (Micro-CT). The iodine atoms remain bound to the polymer as covalent bonds after a series of reactions and exhibit a high level of X-ray opacity. In vitro degradation experiments of the polymer prove that the polymer is degradable., (© 2022 Wiley-VCH GmbH.)

Receptor interacting protein 1 (RIP1) plays important roles not only in cell-death pathways but also in host innate immune responses. In the present study, a RIP1 ortholog named Lc-RIP1 was cloned and characterized in large yellow croaker (Larimichthys crocea). The open reading frame (ORF) of Lc-RIP1 is 2,046 bp, encoding a protein of 681 amino acids (aa), with an N-terminal kinase domain, an RHIM domain, and a C-terminal death domain. Subcellular localization analysis revealed that Lc-RIP1 was a cytosolic protein, which was broadly expressed in examined tissues/organs, and could be up-regulated under poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulation in vivo based on qRT-PCR analysis. Notably, Lc-RIP1 could induce NF-κB, but not IRF3, IRF7 or type I IFN promoter activation. In addition, Lc-RIP1 overexpression could enhance Lc-MAVS, Lc-TRAF3, and Lc-TRAF6 mediated NF-κB promoter activation, and also Lc-TRIF and Lc-MAVS mediated IRF3 promoter activation, whereas suppress Lc-TRIF mediated NF-κB and type I IFN promoter activation, as well as Lc-TRAF3 and Lc-IRF3 mediated IRF3 promoter activation, Lc-IRF3 mediated type I IFN promoter activation and Lc-IRF7 mediated IRF7 promoter activation. These results collectively indicated that Lc-RIP1 function importantly in regulation of host innate immune signaling., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Oral carcinomas is a concerning condition around the world. Globally, it is the 11th most common form of cancer. Over 90% of oral carcinomas are squamous cell carcinomas. Smoking, tobacco intake, smokeless tobacco (snuff or chewing tobacco), excessive sunlight exposure, alcohol, betel nut consumption, human papillomavirus, and reverse end smoking are the most common causes of oral carcinomas. Oral carcinomas are prone to neck lymph mode metastasis, which has an impact on the prognosis of patients and the five-year survival rate. Thus, precise lymph node metastasis and staging of oral carcinomas are critical. With the development of nuclear medicine and molecular imaging, an increasing number of studies have found that Contrast-Enhanced Computed Tomography (CECT) has high diagnostic value for tumors., Methods and Analyses: The reviewers will conduct a thorough search for related literature in 6 online databases, including The Cochrane Library, PubMed, WanFang database, Web of Science, Chinese biomedical literature database, and the China National Knowledge Infrastructure. The authors will obtain full text of studies deemed to be eligible to extract and synthesize data. The present systematic review will be reported in accordance with the Preferred Reporting Project (PRISMA-P) of the 2015 System Review and Meta-Analysis Protocol., Results: The present systematic analysis will pool the results of individual studies to assess the value of CECT in cervical lymph node metastasis of oral carcinomas., Conclusion: The results in the proposed research will determine whether CECT is an efficient diagnostic method for cervical lymph node metastasis of oral carcinomas., Ethics and Dissemination: This study will utilize secondary data from pre-published studies. Therefore, an ethical clearance is not required. The research outcomes shall be disseminated in conference reports and peer-reviewed publications., Osf Registration Number: Oct 13, 2021.osf.io/k5nr9. (https://osf.io/k5nr9/)., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the outcomes of multi-tract percutaneous nephrolithotomy (PCNL) and simultaneous combined single-tract percutaneous nephrolithotomy and flexible ureteroscopic lithotripsy (ECIRS) as treatment for staghorn stones. Methods: The clinical data of patients with staghorn stones who were treated with multi-tract PCNL or single-tract ECIRS in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2015 to December 2019 were retrospectively analyzed. Two group of patients were placed in semisupine-lithotomy position (Galdakao-modified supine Valdivia position). We punctured into the renal calyces guided by ultrasonography. A F6 double J stent and a nephrostomy tube were routinely inserted in both groups. Kidney-ureter-bladder radiography (KUB) or computed tomography (CT) were done within 24 hours and 1 month after procedure to determine stone free rate (SFR). Stone free was defined as no residual stones or residual stones of <4 mm in diameter. The SFR, operating time, intraoperative and postoperative complications, and hospitalization time of the two groups were compared and analyzed. Results: A total of 135 patients were included in the study, 70 patients were female, 65 patients were male. The average age were 50.8 years. A total of 74 patients were managed by multi-tract PCNL, while 61 patients were treated by single-tract ECIRS. The mean stone diameter was (58.5±11.4) mm in the PCNL group and (57.7±11.6) mm in the ECIRS group ( P =0.658). Neither the 24-hour SFR (81.1% vs 80.3%) nor one-month SFR (91.9% vs 90.2%) after procedure was significantly different between the groups (both P >0.05). The operating time was significantly longer in PCNL group compared with ECIRS group [130(100,171) vs 105(90,135) min, P =0.015]. The rate of Clavien-Dindo grade 2 or higher were significantly higher in the PCNL group than the ECIRS group (18.92% vs 1.64%, P <0.01). The PCNL group required longer hospitalization time than the ECIRS group [8 (7, 9) vs 6 (5, 8) d, P <0.01]. Conclusions: Both multi-tract PCNL and single-tract ECIRS treating staghorn stones in semisupine-lithotomy position are safe and effective. The two procedures have comparable SFR. However, the ECIRS group has lower rates of postoperative complications, shorter operating time and hospitalization time.

Little is known about the epidemiology of schizophrenia in the agricultural regions of China. This study examined the 1-month and lifetime prevalence of schizophrenia and their association with socio-demographic factors in Hebei province which is an important agricultural region of China. A multi-stage, stratified, cluster random sampling method was adopted. The diagnosis of schizophrenia was ascertained with the validated Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P/C). Altogether, 23,675 subjects were screened, of whom, 20,884 were included for analyses. The weighted 1-month and lifetime prevalence of schizophrenia were 0.5 % [95 % confidence interval (CI): 0.4-0.5 %] and 0.6 % (95 %CI: 0.5-0.7 %), respectively. Multiple logistic regression analyses found that unmarried marital status [P < 0.001, Odd Ratio(OR)=2.670, 95 %CI:1.767-4.036], lower education level (primary school or below: P = 0.042, OR=2.447, 95 % CI: 1.034-5.933; secondary school: P = 0.002, OR = 4.261, 95 % CI:1.692-10.730), unemployment (P = 0.006, OR=1.870, 95 % CI:1.198-2.920), lower income (P < 0.001, OR=4.017, 95 % CI:2.207-7.310) and family history of psychiatric disorders (P < 0.001, OR=16.278, 95 % CI:10.435-25.393) were independently associated with a higher risk of schizophrenia, while age above 60 years (P = 0.004, OR=0.440, 95 % CI:0.253-0.765) was associated with a lower risk of schizophrenia. The prevalence of schizophrenia appeared to be lower in Hebei province compared to other regions of China or other countries. Socioeconomic factors should be further examined to inform the public health surveillance and policies relevant to schizophrenia in the agricultural regions of China., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs)., Method: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure., Results: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment., Conclusion: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.

Crizotinib, an inhibitor of the hepatocyte growth factor receptor oncogene, has been studied extensively regarding its antitumor and clinically beneficial effects in non-small cell lung cancer (NSCLC). However, crizotinib's effects on cancer cell energy metabolism, which is linked with tumor proliferation and migration, in NSCLC are unclear. Therefore, the present study focused on crizotinib's effect on NSCLC glucose metabolism. Crizotinib's effects on glucose metabolism, proliferation, migration and apoptosis in A549 cells were explored. Several other inhibitors, including 2-DG, rotenone and MG132, were used to define the mechanism of action in further detail. Data showed that crizotinib treatment reduced A549 cell viability, increased glucose consumption and lactate production, while decreased mitochondrial transmembrane potential (Δψm) and ATP production. Crizotinib treatment, combined with rotenone and MG132 treatment, further inhibited ATP production and Δψm and increased reactive oxygen species content. However, crizotinib did not suppress cell proliferation, migration, ATP production, Δψm or mitochondrial-related apoptosis signals further following 2-DG-mediated inhibition of glycolysis. These results indicated that crizotinib induced low mitochondrial function and compensatory high anaerobic metabolism, but failed to maintain sufficient ATP levels. The alternation of metabolic pattern and insufficient ATP supply may serve important roles in the metabolic antitumor mechanism of crizotinib in A549 cells., (Copyright: © Ye et al.)

Objective: Poor mental health is associated with impaired social functioning, lower quality of life, and increased risk of suicide and mortality. This study examined the prevalence of poor general mental health among older adults (aged 65 years and above) and its sociodemographic correlates in Hebei province, which is a predominantly agricultural area of China. Methods: This epidemiological survey was conducted from April to August 2016. General mental health status was assessed using the 12-item General Health Questionnaire (GHQ-12). Results: A total of 3,911 participants were included. The prevalence of poor mental health (defined as GHQ-12 total score ≥ 4) was 9.31% [95% confidence interval (CI): 8.4-10.2%]. Multivariable logistic regression analyses found that female gender [ P < 0.001, odds ratio (OR) = 1.63, 95% CI: 1.29-2.07], lower education level ( P = 0.048, OR = 1.33, 95% CI: 1.00-1.75), lower annual household income ( P = 0.005, OR = 1.72, 95% CI: 1.17-2.51), presence of major medical conditions ( P < 0.001, OR = 2.95, 95% CI: 2.19-3.96) and family history of psychiatric disorders ( P < 0.001, OR = 3.53, 95% CI: 2.02-6.17) were significantly associated with poor mental health. Conclusion: The prevalence of poor mental health among older adults in a predominantly agricultural area was lower than findings from many other countries and areas in China. However, continued surveillance of mental health status among older adults in China is still needed., (Copyright © 2020 Jin, Zhang, Zhang, Rao, Zhang, Cui, Li, Li, Ungvari, Jackson, Li and Xiang.)

Four new species of the subgenus Pedrillia Westwood, 1864 are described from southwest and central China: Zeugophora (Pedrillia) euonymorum sp. nov. , Zeugophora (Pedrillia) flavithorax sp. nov. , Zeugophora (Pedrillia) trifasciata sp. nov. and Zeugophora (Pedrillia) yuae sp. nov. Two species are recorded for the first time in China and redescribed: Zeugophora (Zeugophora) turneri Power, 1863 and Zeugophora (Pedrillia) nigricollis Jacoby, 1885. To date, a total of 35 Zeugophorinae species has been recognized in China., (Kai-Qin Li, Hong-Bin Liang.)

Objective: To investigate the clinical value of the prostate small extracorporeal protein (PSEP) level in the urine in evaluating the therapeutic effect on chronic prostatitis (CP)., Methods: Totally 188 CP patients were treated with minocycline and Ningmitai Capsules in our hospital and regularly returned for follow-up examination from November 2017 to November 2018. Based on the results of treatment after 4 and 8 weeks of medication, we divided the patients into a cured, an effective and an ineffective group and compared the contents of PSEP in the urine samples of the three groups of patients before and after treatment., Results: Compared with the baseline, the PSEP content in the urine after 4 weeks of medication was decreased in the cured group (n = 20) (［3.63 ± 3.81］ vs ［1.16 ± 0.41］ ng/ml, P < 0.05), effective group (n = 85) (［4.13 ± 4.05］ vs ［2.97 ± 2.89］ ng/ml, P > 0.05) and ineffective group (n = 83) (［4.72 ± 2.98］ vs ［3.74 ± 1.31］ ng/ml, P > 0.05), and so was that after 8 weeks of treatment in the cured group (n = 48) (［3.72 ± 3.51］ vs ［0.89 ± 0.37］ ng/ml, P < 0.05), effective group (n = 106) (［4.37 ± 3.93］ vs ［1.83 ± 0.71］ ng/ml, P < 0.05) and ineffective group (n = 34) (［4.61 ± 3.59］ vs ［3.58 ± 1.15］ ng/ml, P > 0.05)., Conclusions: The PSEP level in the urine can be used as an index for clinical evaluation of the therapeutic effect on chronic prostatitis.

Poor sleep quality is associated with negative health outcomes and high treatment burden. This study investigated the prevalence of poor sleep quality and its socio-demographic correlates among older adults in Hebei province, which is a predominantly agricultural region of China. A large-scale cross-sectional epidemiological survey was conducted from April to August 2016. The study used a multistage, stratified, cluster random sampling method. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). A total of 3,911 participants were included. The prevalence of poor sleep quality (defined as PSQI > 7) was 21.0% (95% CI 19.7-22.2%), with 22.3% (95% CI 20.9-23.8%) in rural areas and 15.9% (95% CI 13.4-18.4%) in urban areas. Multivariable logistic regression analyses found that female gender (P < 0.001, OR 2.4, 95% CI 2.00-2.82), rural areas (P = 0.002, OR 1.5, 95% CI 1.14-1.86), presence of major medical conditions (P < 0.001, OR 2.4, 95% CI 2.02-2.96) and family history of psychiatric disorders (P < 0.001, OR 2.7, 95% CI 1.60-4.39) were independently associated with higher risk of poor sleep quality. Poor sleep quality was common among older adults in Hebei province of China. Regular assessment of sleep quality and accessible sleep treatments for older population should be provided in agricultural areas of China.

Objective: To evaluate the thrombolytic effects of recombinant staphylokinase and compare it with those of recombinant streptokinase., Methods: Thirty Chinese experimental miniature pigs were divided into five groups, namely, solvent control group, positive drug control group and three recombinant staphylokinase groups, six in each group. The thrombus of coronary artery was formed by surgical thoracotomy and direct current stimulation in anesthetized animals. Intravenous administration was started after the thrombus of coronary artery was formed for 30 minutes, and the method of first injection and then constant speed infusion by peristaltic pump was used. The solvent control group was injected intravenously with solvent, the positive drug control group was given recombinant streptokinase 4 mg·kg -1 intravenously, and the three recombinant staphylokinase groups were given recombinant staphylokinase at the doses of 4, 2 and 1 mg.kg -1 intravenously. The volume of intravenous injection was 5 ml, which was completed within 1 min, the speed of infusion was 0.5 ml·min -1 , which was completed within 60 min, and the animals were sacrificed 120 minutes later. Before and 30, 60 and 120 min after administration, the venous blood samples were collected. At the end of the experiment, the coronary artery segments of the thrombosis site were taken, and the euglobulin dissolution time (ELT), blood fibrinogen content (FBG), fibrinogen degradation product (FDP) and wound bleeding volume were measured respectively. The coronary thrombolysis rate, myocardial ischemia degree and ischemia range were measured., Results: Compared with the solvent control group, ELT in the experimental group was significantly shortened ( P ＜0.05 or P ＜0.01), FBG degradation in a few experimental animals was more than 20%, FDP was significantly increased ( P ＜0.05 or P ＜0.01), and there was no significant effect on blood pressure and heart rate of small pigs. Compared with the control group, the maximum thrombus area was decreased by 34.3% and 15.4% ( P ＜0.05) in the high and middle dose groups of the experimental group. Compared with the same dose of recombinant streptokinase, recombinant staphylokinase had stronger thrombolytic effect ( P ＜0.05 or P ＜0.01) on the coronary thrombus caused by electrical stimulation, less bleeding side effects and the same effect on the degree and range of myocardial infarction as recombinant streptokinase., Conclusion: Compared with recombinant streptokinase, recombinant staphylokinase has faster thrombolysis speed, higher fibrin specificity and less bleeding side effects. In general, 2 mg.kg -1 recombinant staphylokinase has better efficacy and safety.

Background: Major depressive disorder (MDD) is common among older adults. The epidemiology of MDD is greatly influenced by sociocultural and economic factors. This study examined the 1-month and lifetime prevalence of MDD and its socio-demographic correlates in older adults living in Hebei province, an agricultural area of China., Methods: Multistage, stratified, random sampling was administered between April and August 2016. The diagnosis of MDD was established with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) Axis I Disorders., Results: A total of 3911 participants were enrolled. The 1-month and lifetime prevalence of MDD in older adults was 2.0% (95%CI: 1.6-2.4%) and 3.4% (95%CI: 2.8-4.0%), respectively. Multivariable logistic regression analyses revealed that female gender [P < 0.001, adjusted odds ratio (aOR) = 2.6, 95%CI: 1.53-4.53], presence of comorbid major medical conditions (P < 0.001, aOR = 4.8, 95%CI: 2.17-10.39) and family history of psychiatric disorders (P = 0.013, aOR = 3.4, 95%CI: 1.30-8.96) were independently and significantly associated with higher odds of MDD., Conclusion: The prevalence of MDD in older adults in Hebei province, China, was lower than most findings in China and other countries. Nevertheless, continued surveillance of elderly depression in China along with the development of primary, secondary and tertiary preventative interventions for the elderly with MDD is indicated., Competing Interests: Declaration of Competing Interest There is no conflict of interest related to the topic of this manuscript., (Copyright © 2019. Published by Elsevier B.V.)

The cutting of tooth enamel using a high-speed air-turbine handpiece and carbide bur is a key procedure in oral surgeries, such as the minimally invasive extraction. However, presently little is known about the cutting mechanics and material removal mechanism related to tooth enamel machinability. In this study, the machinability of high-speed enamel cutting with carbide bur is studied by a computer-aided numerical control system. The dynamic cutting forces of enamel of the occlusal, buccal/lingual, and proximal surfaces were measured by the force measuring system. The force ratio, cutting torque, rotating speed, specific cutting energy, and bur wear were analyzed. The microstructure of enamel and carbide burs was observed by the scanning electron microscope, and the relationship between enamel microstructures and machinability was further analyzed. The results show that during the high-speed enamel cutting with carbide bur, the chip thickness is on the nano-scale, and the plastic deformation of the machined surface is obvious. With increased material removal rate, the cutting force, torque, specific cutting energy, and bur wear increases accordingly, whereas the rotating speed decelerates (p < 0.05). The different angles between the cutting direction and the axial direction of the enamel rods give rise to the large differences in the cutting mechanics and mechanism of the proximal, buccal/lingual, and occlusal surfaces of the teeth. When the cutting direction is parallel, vertical, and oblique 45° to the axial direction of the enamel rods, the force required for material fracture and crack propagation increases, and the cutting force increases as a consequence. Parallel and oblique 45° cutting are the main modes of tooth segmentation in the minimally invasive extraction. In comparison with the parallel cutting mode, the cutting force, torque, and cutting ratio of the oblique 45° cutting mode can be significantly increased, and the tool wear is obviously accelerated. This is the lowest priority in segmentation surgery, hence the problems of overload and temperature rise need to be considered. The cutting mechanics and cutting mechanism obtained in this study will provide scientific process guidance for dental cutting operations with the air-turbine handpiece driving bur., Competing Interests: Declaration of competing interest The authors claim no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Few studies have estimated the prevalence and correlates of bipolar disorder (BP) in agricultural areas of China. This study examined the one-month and lifetime prevalence of BP, its subtypes and socio-demographic factors in the adult population of Hebei province, a predominantly agricultural area of China., Methods: A multistage, stratified, cluster random sampling method was used to estimate the prevalence and correlates of BP in adults in Hebei province, China. The expanded version of the 12-item General Health Questionnaire (GHQ-12) and the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P/C) were administered to establish the diagnosis of BP., Results: A total of 20,884 participants were screened. The weighted lifetime prevalence of BP, BP type I (BP-I), type II (BP-II), and BP not otherwise specified (BP-NOS) were 0.20% (95% CI: 0.14-0.26%), 0.13% (95% CI: 0.08-0.18%), 0.03% (95% CI: 0.009-0.06%) and 0.03% (95% CI: 0.009-0.06%), respectively. The weighted one-month prevalence estimates were 0.12% (95% CI: 0.08-0.17%) for BP, 0.07% (95% CI: 0.04-0.11%) for BP-I, 0.03% (95% CI: 0.006-0.05%) for BP-II, and 0.02% (95% CI: 0.003-0.04%) for BP-NOS. Multiple Poisson regression analysis revealed that positive family history of any psychiatric disorder (P<0.001, OR=6.48, 95% CI: 2.53-16.56) was significantly associated with greater risk of BP., Conclusion: The prevalence of BP in Hebei province appears lower than in most areas of China and other countries. Continued surveillance of BP in China along with the development of primary and tertiary preventative interventions for psychiatric disorders is indicated., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest concerning this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To study the relationship of the content of prostatic exosomal protein (PSEP) in the urine with the counts of WBCs and small particles of lecithin (SPL) in the EPS and NIH-CPSI in patients with chronic prostatitis., Methods: We collected mid-stream urine samples from 367 chronic prostatitis patients in the Department of Andrology of the General Hospital of Eastern Theater Command from November 2017 to August 2018. We measured the content of PSEP in the urine, counted WBCs and SPLs in the EPS of the patients, obtained their NIH-CPSI scores, and analyzed the correlation of the PSEP level with the WBC and SPL counts and NIH-CPSI scores of the patients., Results: The PSEP level in the urine was elevated with the increase of the WBC count in the EPS of the patients (r = 0.19, P = 0.047) but not significantly correlated with the SPL count in the EPS (r = 0.02, P = 0.48). A significant correlation was observed between the PSEP level and the NIH-CPSI scores of the patients (r = 0.31, P = 0.02)., Conclusions: The PSEP content in the urine can be used as an indicator in the clinical diagnosis and assessment of the inflammation degree of chronic prostatitis.

Background: Major depressive disorder (MDD) is a common psychiatric disorder which is associated with significant disability and psychosocial factors. There are only few epidemiological studies of MDD in economically underdeveloped regions of China. This study examined the 1-month and lifetime prevalence of MDD and their sociodemographic correlates in Hebei province, China., Methods: Using multistage, stratified and random sampling, the study was conducted between April and August 2016. The diagnosis of MDD was established using the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition., Results: The weighted 1-month and lifetime prevalence of MDD were 0.9% (95%CI: 0.8-1.1%) and 1.6% (95%CI: 1.4-1.8%), respectively in the sample of 14,654 adult participants. Multiple logistic regression analysis revealed that the age group of 45-59 years (P < 0.001, OR=3.206, 95%CI:1.693-6.072), female gender (P < 0.001, OR=2.171, 95%CI: 1.522-3.097), married marital status (P < 0.001, OR=0.328, 95%CI: 0.198-0.545), college educational level or higher (P = 0.006, OR=0.145, 95%CI: 0.037-0.573), employment (P = 0.010, OR=2.305, 95%CI: 1.220-4.353), major medical conditions (P < 0.001, OR=3.758, 95%CI: 2.607-5.418) and family history of psychiatric disorders (P < 0.001, OR=3.947, 95%CI: 2.203-7.071) were significantly associated with MDD., Conclusion: The prevalence of MDD in Hebei province was found to be lower than in most areas of China and other countries. Further studies are warranted to confirm the low prevalence of MDD in other economically underdeveloped regions of China., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.

A homotritopic pillar[5]arene (H3) containing adenine units was synthesized and employed to interact with a uracil derivative (6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)hexanenitrile, G) to form a hyperbranched supramolecular polymer. The hyperbranched supramolecular polymer showed a dual stimulus response both to heat and acid/base. The cooperative host-guest binding and hydrogen-bond interactions play a key role in the supramolecular polymerization.

Objective: Growing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this., Methods: Resting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups., Results: The cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula., Conclusions: This study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD., (© 2018 John Wiley & Sons Ltd.)

Objective: To detect the contents of prostaticexosomal protein (PSEP) in the first- and mid-stream urine and assess their clinical value in the diagnosis of chronic prostatitis (CP)., Methods: This study included358 male outpatientsat Nanjing General Hospital from November 2017 to May 2018, 269 diagnosed with and the other 89 without CP. Wemeasured the contents of PSEP in the first- and mid-stream urine samples collected from the subjectsby ELISA anddetermined the sensitivity and specificity, and total coincidence rate ofthe PSEPcontents in the diagnosis of CP. Using the ROC curve, we compared the PSEP levels in the two different urine samples and the results of diagnosis of CPbetween the PSEP detection method and clinical diagnostic criteria., Results: No statistically significant difference was observed between the contents of PSEP in the first- and mid-stream urine samples (［3.82 ± 3.74］ vs ［3.77 ± 3.90］ ng/ml, P = 0.46). In the diagnosis of CP, the PSEP contents in the first- and mid-stream urine samples manifested a sensitivity of 81.41% vs 86.99%, a specificity of 89.89% vs 88.76%, and a total coincidence rate of 83.52% vs 87.43%., Conclusions: Both the content of PSEP in the first-stream and that in the mid-stream urine can be used as auxiliarydiagnostic indicators of chronic prostatitis, bothwith high sensitivity and specificity.

In 2006, the "unlocking program" was implemented in Hebei province, China to promote the human rights for people with severe mental illness who were physically restrained at home. We assessed the long term outcomes of the "unlocking program" following the provision of hospital and community psychiatric care over 10 years and explored their associated factors. A total of 107 patients with severe mental illness who were "unlocked" in the program were included. Outcome measures were collected with standardized rating scales at 2 separate time points in August 2012 and November 2016. Poor outcome was defined either as being relocked, or missing to follow up or death. In 2012, 36 patients (33.6%) had poor outcomes. Poor outcome was positively associated with follow-up length and less caregiver burden at baseline. By 2016, 53 patients (49.5%) were found to have poor outcomes. There was only a trend of positive association between poor outcome and less caregiver burden at baseline. Poor long-term outcomes were common in patients with severe mental illness following the "unlocking program". Evidence-based treatment strategies and mental health services to improve the outcomes and protect the human rights of patients subjected to being locked in the community are urgently needed.

5-fluorouracil (5-FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5-FU-based chemotherapy. Bufalin, a type of steroid with anti-tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti-tumor effect of 5-FU, the present study examined the combined effects of bufalin with 5-FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MTT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis-associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5-FU in HCT116 cells via the induction of the mitochondrial apoptotic pathway. Additionally, bufalin combined with 5-FU reduced the expression levels of anti-apoptotic proteins, such as Mcl-1, XIAP and Bcl-2 and upregulated the levels of the pro-apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock-down Bax. It was determined that the synergistic effect between 5-FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5-FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.

Objective: To study the protective effect of lipoic acid (LA) on the spermatogenic function of the male rats with oligoasthenozoospermia induced by ornidazole (ORN)., Methods: Seventy male SD rats were equally randomized into groups A (solvent control: 1 ml 0.5% CMC-Na + 1 ml olive oil), B (low-dose ORN model: 400 mg/kg ORN suspension + 1 ml olive oil), C (low-dose ORN + low-dose LA treatment: 400 mg/kg ORN + 50 mg/kg LA), D (low-dose ORN + high-dose LA treatment: 400 mg/kg ORN + 100 mg/kg LA), E (high-dose ORN model: 800 mg/kg ORN suspension + 1 ml olive oil), F (high-dose ORN + low-dose LA treatment: 800 mg/kg ORN + 50 mg/kg LA), and G (high-dose ORN + high-dose LA treatment: 800 mg/kg ORN + 100 mg/kg LA), and treated respectively for 20 successive days. Then all the rats were sacrificed and the weights of the body, testis, epididymis and seminal vesicle obtained, followed by calculation of the organ index, determination of epididymal sperm concentration and motility, and observation of the histomorphological changes in the testis and epididymis by HE staining., Results: Compared with group A, group E showed significantly decreased body weight (［117.67 ± 11.53］ vs ［88.11 ± 12.65］ g, P < 0.01) and indexes of the testis (［1.06 ± 0.12］ vs ［0.65 ± 0.13］ %, P < 0.01) and epididymis (［0.21 ± 0.03］ vs ［0.17 ± 0.01］ %, P < 0.01). In comparison with group E, group F exhibited remarkable increases in the epididymal index (［0.17 ± 0.01］ vs ［0.20 ± 0.02］ %, P < 0.01), and so did group G in the body weight (［88.11 ± 12.65］ vs ［102.70 ± 16.10］ g, P < 0.05) and the indexes of the testis (［0.65 ± 0.13］ vs ［0.95 ± 0.06］ %, P < 0.01) and epididymis (［0.17 ± 0.01］ vs ［0.19 ± 0.02］ %, P < 0.05), but no obvious difference was observed in the index of seminal vesicle among different groups. Compared with group A, group B manifested significant decreases in sperm motility (［74.12 ± 8.73］ vs ［40.25 ± 6.08］ %, P < 0.01), and so did group E in sperm count (［38.59 ± 6.40］ vs ［18.67 ± 4.59］ ×105/100 mg, P < 0.01) and sperm motility (［74.12 ± 8.73］ vs ［27.58 ± 8.43］ %, P < 0.01). Sperm motility was significantly lower in group B than in C and D (［40.25 ± 6.08］ vs ［58.13 ± 7.62］ and ［76.04 ± 8.44］%, P < 0.01), and so were sperm count and motility in group E than in F and G (［18.67 ± 4.59］ vs ［25.63 ± 9.66］ and ［29.92 ± 4.15］ ×105/100 mg, P < 0.05 and P < 0.01; ［27.58 ± 8.43］ vs ［36.56 ± 11.08］ and ［45.05 ± 9.59］ %, P < 0.05 and P < 0.01). There were no obvious changes in the histomorphology of the testis and epididymis in groups A, B, C and D. Compared with group A, group E showed necrotic and exfoliated spermatogenic cells with unclear layers and disorderly arrangement in the seminiferous tubules and remarkably reduced sperm count with lots of noncellular components in the epididymal cavity, while groups F and G exhibited increased sperm count in the seminiferous tubules and epididymis lumen, also with exfoliation, unclear layers and disorderly arrangement of spermatogenic cells, but significantly better than in group E., Conclusions: LA can reduce ORN-induced damage to the spermatogenetic function of rats, improve sperm quality, and protect the reproductive system.

Objective: To investigate the factors associated with the occurrence of transplant renal artery stenosis (TRAS)., Methods: A retrospective analysis was conducted in 26 recipients who developed TRAS and 40 concurrent renal recipients without TRAS. We also conducted a nested case-control study in 14 patients with TRAS (TRAS-SD group) and another 14 non-TRAS recipients who received the allograft from the same donor (non-TRAS-SD group)., Results: Compared with those in the concurrent recipients without TRAS, acute rejection (AR) occurred at a significantly higher incidence (P=0.004) and the warm ischemia time (WIT) was significantly longer (P=0.015) and the level of high?density lipoprotein cholesterol (HDL--C) significantly lower (P=0.009) in the recipients with TRAS. Logistic regression analysis suggested that AR (P=0.007) and prolonged WIT (P=0.046) were risk factors of TRAS while HDL-C (P=0.022) was the protective factor against TRAS. In recent years early diagnosis of TRAS had been made in increasing cases, the interval from transplantation to TRAS diagnosis became shortened steadily, and the recipients tended to have higher estimated glomerular filtration rate at the time of TRAS diagnosis., Conclusion: Apart from the surgical technique, AR and prolonged WIT are also risk factors of TRAS while a high HDL-C level is the protective factor against TRAS. The improvement of the diagnostic accuracy by ultrasound is the primary factor contributing to the increased rate of early TRAS diagnosis in recent years.

Our previous study demonstrated that there have been changes in the patterns of prescription antipsychotic use in China over the period from 2002 to 2012. The aim of this study was to evaluate whether time trends were present for the prescription of anticholinergic medications (ACMs) during the observation period. A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were surveyed in 2002, 2006 and 2012. Basic socio-demographic and clinical characteristics and the prescription of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The frequency of ACM prescription was 25.9% in the whole sample (29.5%, 21.6%, and 27.4% in 2002, 2006 and 2012, respectively). In addition, different temporal trends were observed across age groups. Multiple logistic regression analysis of the entire sample showed that ACM prescriptions were predicted by females, outpatients, patients receiving high doses of antipsychotic medication, select study years, benzodiazepine users, patients displaying extrapyramidal side effects, as well as antipsychotic prescription patterns. Although there was more widespread use of second-generation antipsychotics over the past decade, the frequency of ACM use only slightly decreased. How to use ACM appropriately is still a therapeutic issue that needs to foster evidence-based prescription practice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

An extract from a traditional Chinese herb, Marsdeniae tenacissima (trade name, Xiao-Ai-Ping) has been approved for use on the Chinese market as a cancer chemotherapeutic agent for decades. Previous studies have demonstrated the cytostatic and pro-apoptotic effects of M. tenacissima extract (MTE) in multiple cancer cells. However, the contributions of MTE to the proliferation and apoptosis of hepatoma carcinoma cells and the underlying mechanisms remain unclear. In the present study, Bel-7402 cells were incubated with increasing concentrations of MTE ranging from 0-320 µl/ml to explore the effects and potential mechanisms of MTE on the proliferation and apoptosis of Bel-7402 cells. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt and propidium iodide (PI)-stained flow cytometry assays demonstrated that MTE significantly suppressed the proliferation of Bel-7402 cells in a dose-dependent manner by arresting the cell cycle at S phase (P<0.05). Annexin V-fluorescein isothiocyanate PI-stained flow cytometry confirmed the significantly pro-apoptotic effect of MTE at both 160 and 240 µl/ml (P<0.001). Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that MTE (both 160 and 240 µl/ml) induced a significant downregulation of B-cell lymphoma (Bcl)-2 (P<0.01), upregulation of Bcl-2-associated X protein (P<0.01) and activation of caspase-3 (P<0.05). Furthermore, a significant downregulation of murine double minute-2 (MDM2) (P<0.001) and activation of p53 (P<0.001) in Bel-7402 cells following treatment with 160 or 240 µl/ml MTE was observed, accompanied by the inhibition of the nuclear factor (NF)-κB pathway (P<0.001). These results suggested that MTE inhibited growth and exhibited pro-apoptotic effects in Bel-7402 cells, which was mediated by downregulation of the MDM2-induced p53-dependent mitochondrial apoptosis pathway and blocking the NF-κB pathway. Overall, these data serve as preliminary identification of the significant roles of MTE in hepatic carcinoma cells, and suggest that MTE may be a promising candidate for hepatocellular carcinoma therapy.

We have carried out the investigation on a sponge-derived fungus,which was identified as Emericella variecolor from the south sea of China. Two new chemical constituents,(+)-2-acetyl-dihydroterrein (1) and (+)-3-acetyl-dihydroterrein (2),with four known compounds,anditomin (3),andilesin A (4),andilesin C (5) and andilesin B (6),were isolated from this fungus by column chromatography over silica gel, Sephadex LH-20, and ODS. The structures of 1 and 2 were elucidated by spectroscopic methods including NMR,HR-ESI-MS,and CD., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To investigate the value of real-time RNA simultaneous amplification and testing (SAT) in the detection of Ureaplasma urealyticum (UU) in the semen of infertile males and its clinical significance., Methods: We collected semen samples from 542 infertility patients and 120 normal fertile men as controls in the Andrology Clinic of Nanjing General Hospital from March to September 2015. We detected UU infection in the samples using the culture method and SAT technology, respectively., Results: All the UU positive cases (except 4 false positive cases) detected by the culture method were also shown to be positive in SAT. The UU detection rate of SAT was significantly higher than that of the culture method both in the infertility patients (54.1 vs 19.7%, P<0.05) and in the normal controls (42.5 vs 12.5%, P<0.05)., Conclusions: SAT is a rapid and accurate method for detecting UU infection in semen samples, with a higher sensitivity and accuracy than the culture method, and it can also be used to evaluate the therapeutic effects. However, the culture method has its own advantages, such as low requirement of technical equipment, easy operation, and possibility of drug sensitivity test at the same time. Therefore, SAT and the culture method can be used alternatively according to the clinical need.

Minimally invasive endoscopic resection has been rapidly adopted as a new technique for treating patients with gastric submucosal tumors (SMTs) originating in the muscularis propria (MP) layer. This study was conducted to evaluate the information obtained from endoscopic ultrasonography (EUS) to determine the appropriate endoscopic dissection method for treating SMTs originating in the MP layer. Between February 2014 and May 2016, a total of 50 patients with gastric SMTs originating in the MP layer were enrolled in this study. The clinical features of the patients and their endoscopic, EUS, and histopathologic findings, as well as their postoperative follow-up data, were analyzed in this retrospective study. The mean age of the patients was (55.0±10.2) years, and the male/female ratio was 17:33. Endoscopic submucosal dissection (ESD) was performed on 43 patients and an endoscopic full-thickness resection (EFR) was performed on seven patients. The most frequent location for an SMT was in the upper body region of the stomach (n=16), and the most common pathological diagnosis was a gastrointestinal stromal tumor (GIST) (n=32). The overall rates for complete resection were 95.3% (41/43) and 100.0% (7/7) when the SMTs were treated by ESD and EFR, respectively. The presence of a complete tumor capsule was significantly associated with a complete resection (P=0.001). Of the cases treated by ESD, nine patients developed perforation, one of whom required laparoscopic surgery. The remaining patients were closed with clips or purse-string sutures. The presence of an MP2-type tumor (P=0.018) and a wide connection with the MP layer (P=0.044) were significantly associated with perforation. A preoperative evaluation of the integrity and the location of a tumor capsule and the length of the tumor connection with the MP layer by EUS can improve the complete resection rate and reduce the occurrence of intraoperative complications. Tumors with a complete capsule originating from the superficial MP layer or with a narrow connection with the MP layer are appropriate candidates for treatment by ESD.