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.

Objective:To investigate the distribution characteristics and analyze the clinical significance of dermatophagoides pteronyssinus allergen components in children with allergic rhinitis and asthma in Shenzhen.Methods:This study was a cross-sectional study. The clinical data of children with allergic rhinitis and asthma induced by dust mites admitted to the allergy clinic of Shenzhen Children′s Hospital from 2021 to 2024 were collected and the serum sIgE levels of dermatophagoides pteronyssinus, dermatophagoides farinae (Der p, Der f) and dermatophagoides pteronyssinus components (Der p 1, Der p 2, Der p 10, Der p 23) were detected by magnetic bead chemiluminescence method. The correlation between dermatophagoides pteronyssinus allergen components and clinical data of children was analyzed. According to the diagnosis, the children were divided into allergic rhinitis (AR) group and AR with asthma (ARAS) group. According to the age, the children were divided into preschool age (5 years ≤age<7 years), school age (7 years ≤age<10 years) and adolescence (10 years ≤age≤15 years). The expression differences of dermatophagoides pteronyssinus components among AR group and ARAS group and different age groups were compared.Results:A total of 314 children with allergic rhinitis and asthma caused by dust mites were included in the study, of whom 112 were male and 202 were female. There were 188 cases of AR and 126 cases of ARAS, aged 5-15 years, with a median age of 7.54 years and an average age of (8.02±2.24) years. BMI was 13.89-31.76 kg/m 2,the median BMI was 15.87 kg/m2 and average BMI was (16.55±3.05) kg/m2. There was not statistically significant difference in gender, age, BMI, blood eosinophils, blood basophils, FeNO, FVC and FEV1 between the AR group and the ARAS group ( P>0.05). There was significant difference in FEV1/FVC and small airway function indexes MMEF, MEF75%, MEF50% and MEF25% between the AR group and the ARAS group ( P<0.05). In the 314 children, the dermatophagoides pteronyssinus allergen components sensitization rates were in the order of Der p 1 (97.1%), Der p 2 (89.8%), Der p 23 (55.1%), Der p 10 (8.6%), and the difference in the positive rate was statistically significant (χ 2=658.31, P<0.001). There was not significant difference in Der p 1, Der p 2 and Der p 10 among children of different ages ( P>0.05). There was significant difference in Der p 23 among children of different ages (χ 2=7.29, P=0.03). A correlation analysis showed that Der p, Der f, Der p 1 and Der p 2 had a high positive correlation ( P<0.001). Eosinophils are positively correlated with Der p, Der f, Der p 1, Der p 2, Der p 10 and Der p 23 ( P<0.001). FeNO is positively correlated with Der p, Der f, and Der p 23 ( P<0.05). Small airway function indicators MMEF, MEF50% and MEF25% are negatively correlated with Der p, Der f and Der p 1 ( P<0.05). The sIgE levels of Der p, Der f, Der p 1, Der p 2 and Der p 10 in the AR group were significantly lower than those in the ARAS group ( P<0.05). In the ARAS group, 120 cases (95.24%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 71 cases (56.35%) showed positive results for at least 3 dermatophagoides pteronyssinus components. In the AR group, 171 cases (90.96%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 94 cases (50.00%) showed positive results for at least 3 dermatophagoides pteronyssinus components. Conclusion:Der p 1, Der p 2 and Der p 23 may be the main dermatophagoides pteronyssinus allergen components that induce allergic rhinitis and asthma in Shenzhen City. The elevation of sIgE levels in the dermatophagoides pteronyssinus components can aggravate the severity of lower airway eosinophilic inflammation and airway obstruction. Attention should be paid to the detection of dermatophagoides pteronyssinus components in children with poor response to dust mite-allergen specific immunotherapy.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To investigate the distribution characteristics and analyze the clinical significance of dermatophagoides pteronyssinus allergen components in children with allergic rhinitis and asthma in Shenzhen.Methods:This study was a cross-sectional study. The clinical data of children with allergic rhinitis and asthma induced by dust mites admitted to the allergy clinic of Shenzhen Children′s Hospital from 2021 to 2024 were collected and the serum sIgE levels of dermatophagoides pteronyssinus, dermatophagoides farinae (Der p, Der f) and dermatophagoides pteronyssinus components (Der p 1, Der p 2, Der p 10, Der p 23) were detected by magnetic bead chemiluminescence method. The correlation between dermatophagoides pteronyssinus allergen components and clinical data of children was analyzed. According to the diagnosis, the children were divided into allergic rhinitis (AR) group and AR with asthma (ARAS) group. According to the age, the children were divided into preschool age (5 years ≤age<7 years), school age (7 years ≤age<10 years) and adolescence (10 years ≤age≤15 years). The expression differences of dermatophagoides pteronyssinus components among AR group and ARAS group and different age groups were compared.Results:A total of 314 children with allergic rhinitis and asthma caused by dust mites were included in the study, of whom 112 were male and 202 were female. There were 188 cases of AR and 126 cases of ARAS, aged 5-15 years, with a median age of 7.54 years and an average age of (8.02±2.24) years. BMI was 13.89-31.76 kg/m 2,the median BMI was 15.87 kg/m2 and average BMI was (16.55±3.05) kg/m2. There was not statistically significant difference in gender, age, BMI, blood eosinophils, blood basophils, FeNO, FVC and FEV1 between the AR group and the ARAS group ( P>0.05). There was significant difference in FEV1/FVC and small airway function indexes MMEF, MEF75%, MEF50% and MEF25% between the AR group and the ARAS group ( P<0.05). In the 314 children, the dermatophagoides pteronyssinus allergen components sensitization rates were in the order of Der p 1 (97.1%), Der p 2 (89.8%), Der p 23 (55.1%), Der p 10 (8.6%), and the difference in the positive rate was statistically significant (χ 2=658.31, P<0.001). There was not significant difference in Der p 1, Der p 2 and Der p 10 among children of different ages ( P>0.05). There was significant difference in Der p 23 among children of different ages (χ 2=7.29, P=0.03). A correlation analysis showed that Der p, Der f, Der p 1 and Der p 2 had a high positive correlation ( P<0.001). Eosinophils are positively correlated with Der p, Der f, Der p 1, Der p 2, Der p 10 and Der p 23 ( P<0.001). FeNO is positively correlated with Der p, Der f, and Der p 23 ( P<0.05). Small airway function indicators MMEF, MEF50% and MEF25% are negatively correlated with Der p, Der f and Der p 1 ( P<0.05). The sIgE levels of Der p, Der f, Der p 1, Der p 2 and Der p 10 in the AR group were significantly lower than those in the ARAS group ( P<0.05). In the ARAS group, 120 cases (95.24%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 71 cases (56.35%) showed positive results for at least 3 dermatophagoides pteronyssinus components. In the AR group, 171 cases (90.96%) showed positive results for at least 2 dermatophagoides pteronyssinus components, while 94 cases (50.00%) showed positive results for at least 3 dermatophagoides pteronyssinus components. Conclusion:Der p 1, Der p 2 and Der p 23 may be the main dermatophagoides pteronyssinus allergen components that induce allergic rhinitis and asthma in Shenzhen City. The elevation of sIgE levels in the dermatophagoides pteronyssinus components can aggravate the severity of lower airway eosinophilic inflammation and airway obstruction. Attention should be paid to the detection of dermatophagoides pteronyssinus components in children with poor response to dust mite-allergen specific immunotherapy.

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