Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Objective To investigate the effects of preoperative symptom duration(DOS)and histolog-ical changes in the nucleus pulposus on the outcome of minimally invasive transforaminal lumbar interbody fu-sion(MIS-TLIF)in patients with lumbar degenerative diseases.Methods A total of 162 patients in this hos-pital with lumbar degenerative diseases who underwent MIS-TLIF surgery from March 2022 to June 2023 were prospectively enrolled.According to DOS,they were divided into the short-term DOS group(group S,DOS＜12 months)and the long-term DOS group(group L,DOS ≥ 12 months).Nucleus pulposus tissue was collected for hematoxylin-eosin(HE)staining to observe tissue morphology,immunohistochemical staining was used to detect protein expression of interleukin(IL)-6,IL-1,and tumor necrosis factor-α(TNF-α),and re-al-time fluorescence quantitative PCR(qPCR)was used to analyze the expression levels of IL-6 mRNA,IL-1 mRNA,and TNF-α mRNA.The Oswestry Disability Index(ODI)score and Visual Analog Scale(VAS)score for lower back pain,leg pain,and numbness before surgery and at 1,3,6,12 months after surgery were com-pared to evaluate clinical efficacy.Results There was no significant difference in baseline data between Group S and Group L(P＞0.05).HE staining showed that the degeneration,cracking,and inflammatory infiltration of the nucleus pulposus in group L were more pronounced than those in group S;The results of immunohisto-chemistry and qPCR showed that the protein expressions of IL-6,IL-1,and TNF-α in group L were more obvi-ously and their mRNA expression levels were significantly higher than those in group S(P＜0.05).Both groups showed a significant decrease in postoperative ODI,VAS score for lower back pain,VAS score for leg pain,and VAS score for numbness compared to preoperative levels(P＜0.05).However,three months after surgery,the ODI,VAS score for lower back pain and numbness in group S were lower than those in group L(P＜0.01);Six months after surgery,the VAS score for back pain,leg pain,and numbness in group S were lower than those in group L(P＜0.01);12 months after surgery,the VAS score for numbness in group S was still lower than that in group L(P＜0.01).Subgroup analysis of patients with cauda equina syndrome showed that at 3 months after surgery,the VAS score for lower back pain in group S were lower than that in group L(P＜0.01);six months after surgery,the VAS score for leg pain in group S was lower than that in group L(P＜0.01);12 months after surgery,the VAS score for back pain,leg pain,and numbness in group S were lower than those in group L(P＜0.01).Conclusion Long-term DOS is significantly associated with high ex-pression of inflammatory factors in the nucleus pulposus and delayed long-term functional recovery.Early sur-gical intervention can optimize the clinical outcomes of patients with lumbar degenerative diseases.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

OBJECTIVE： To study the effects of serglycan （SRGN） on drug resistance of ovarian cancer and its mechanism. METHODS： Gene expression profile interactive analysis tool （GEPIA） was used to extract related data set of ovarian cancer and analyze the difference of mRNA expression of SRGN between normal ovary tissue and ovarian cancer tissue. Gene expression database （GEO） was adopted to obtain the difference of the mRNA expression of SRGN in cisplatin sensitive and cisplatin resistant cell lines （A2780）. STRING online database was used to screen proteins interacting with SRGN （confidence degree： 0.900， interactors： 10）. Adopted biological information annotation database （DAVID） to analysis Kyoto encyclopedia of genes and genomers（KEGG）metabolism pathway to predict the potential pathways of SRGN regulating drug resistance of ovarian cancer. Medical ontology information retrieval platform COREMINE was used to mine the biological processes of significant relationship of SRGN and ovarian cancer with drug resistance. RESULTS： mRNA expression of SRGN in ovarian cancer tissue was significantly higher than normal ovarian tissue （P＜0.05）. mRNA expression of SRGN in cisplatin resistant ovarian cancer was significantly higher than cisplatin sensitive ovarian cancer （P＜0.001）. 10 proteins interacting with SRGN were screened， including albumin， transforming growth factor β1， platelet factor 4， fibrinolysin and vascular endothelial growth factor A. SRGN participated in KEGG metabolism pathway of regulating drug resistance of ovarian cancer， including HIF1α pathway， cytokine-cytokine receptor pathway， coagulation and complement cascades pathway， etc. Biological processes included gene expression， cell growth， apoptosis and cell death. CONCLUSION： SRGN mediates drug resistance of ovarian cancer， which is associated with HIF1α signaling pathway and cytokine-cytokine receptor pathway.

Objective To observe the effect of needle warming moxibustion on cognitive dysfunction after stroke. Methods 76 stroke patients with cognitive dysfunction were randomly divided into treatment group (n=38) and control group (n=38). The treatment group received needle warming moxibustion and routine rehabilitation for 4 weeks, while the control group only received routine rehabilitation. They were assessed with Montreal Cognitive Assessment (MoCA) and activities of daily living (ADL) scale before and after treatment. Results The score of MoCA and ADL improved in both groups (P<0.05), and improved more in the treatment group than in the control group (P<0.05) after treatment. Conclusion Needle warming moxibustion could improve cognitive function in patients after stroke and activities of daily living.

Objective To observe the effect of intelligent trunk intensive training on motor and balance for patients with stroke. Methods 80 stroke patients were divided into treatment group (n=40) and control group (n=40) randomly. Both groups accepted routine rehabilitation,and the treatment group accepted intelligence trunk intensive training in addition for 6 weeks. They were assessed with Rivermead Movement Index (RMI), the Berg Balance Scale (BBS), Sheikh trunk control ability evaluation before and after treatment. Results All the scores improved after treatment in both groups (P<0.001), and improved more in the treatment group than in the control group (P<0.001).The score of trunk control positively correlated with the score of RMI and BBS respectively (r=0.576, r=0.592, P<0.05). Conclusion Intelligent trunk intensive training can further improve the motor and balance of patients with stroke.

Objective To investigate the effects of rehabilitation stroke unit on patients with shoulder-hand syndrome after stroke. Methods 90 stroke patients with shoulder-hand syndrome were divided into two groups: control group (45 cases) was treated with conventional treatment and experimental group (45 cases) was incorporated into the rehabilitation stroke unit. The therapeutic course was 6 weeks.Brunnstrom stage, Fugl-Meyer assessment (FMA) and modified Barthel index (MBI) were used to assess the degree of the motor function of upper limb and hand, and activities of daily living (ADL), and the total clinical efficacy were evaluated. Results The motor function of upper limb and hand and ADL improved in both groups after treatment (P<0.05), while the experimental group was significantly superior to the control group (P<0.05). Conclusion Rehabilitation stroke unit has preferable effect on shoulder-hand syndrome after stroke.