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.

Clinical research is usually aimed at and guided by therapeutic efficacy. Clarifying the placebo effect and the nocebo effect from treatment outcomes is an important issue in clinical research. This paper reviews the meaning of the placebo effect， suggesting that factors that may produce the placebo effect in clinical practice include past experience associations， patient expectations， suggestion， and doctor-patient relationships. It also summarizes the characteristics of the nocebo effect， its influencing factors， and its impact on clinical prognosis. Combining the characteristics of traditional Chinese medicine， this paper explores the design of acupuncture clinical trials that can reflect the measurement of the placebo effect， attempting to provide a clearer interpretation of the placebo effect in the evaluation of acupuncture efficacy in traditional Chinese medicine. Taking primary insomnia as an example， a prospective randomized placebo-controlled trial is designed to observe and evaluate the relationship between the treatment effects of acupuncture and the placebo effect in different patients under the treatment of the same doctor. Group comparisons will help better distinguish clinical effects in different situations. The authors also attempt to explore the responsive population to the placebo effect and the effects of placebos in different populations.

There has been a growing amount of evidence that a balanced blood component transfusion with roughly equal ratio of units of packed red blood cells,fresh frozen plasma,and platelets leads to better outcomes in massive transfusion re-suscitation of trauma victims.Therefore,the great interest of massive transfusion protocol(MTP)with whole blood was a-roused.Low titer group O whole blood(LTOWB)is implemented in routine use for civilian prehospital ambulance services in large trauma centers of most European and American countries nowadays.There is a growing body of evidence to date to support that early use of LTOWB in patients with life-threatening bleeding improve their survival.In view of the current situ-ation of whole blood supply in our country,most trauma resuscitation guidelines still recommend balanced component trans-fusion for MTPs in the early stage of resuscitation.The research and application of LTOWB abroad will be introduced in this article.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.

Objective To investigate the effects of glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) on glioma growth and macrophage infiltration. Methods Initially, the expression of GPIHBP1 in glioma samples and macrophage infiltration were analyzed using TCGA database, and these bioinformatics results were validated in clinical tissue samples. A stable glioma cell line overexpressing GPIHBP1 was then established to further explore the effects of GPIHBP1 overexpression on glioma cell proliferation, apoptosis, migration, and invasion. Finally, the impact of GPIHBP1 overexpression on tumor growth and macrophage infiltration was verified through xenograft experiments. Results TCGA database analysis revealed that GPIHBP1 expression was higher in low-grade gliomas compared to normal tissues, while it was lower in high-grade gliomas. Additionally, the expression level of GPIHBP1 in low-grade gliomas was higher than in high-grade gliomas, which was confirmed by immunohistochemistry (IHC). Western blot analysis confirmed the successful construction of the GPIHBP1-overexpressing glioma cell line. CCK-8, flow cytometry, scratch and Transwell assays demonstrated that the proliferation, migration and invasion capabilities of the stable cell line were reduced compared to the control group. Xenograft experiments further showed that the tumor growth and macrophage infiltration were decreased in the stable cell line. Conclusion The differential expression of GPIHBP1 in different grades of gliomas may be associated with tumor progression. Overexpression of GPIHBP1 can inhibit glioma growth, possibly by influencing the tumor microenvironment and promoting the polarization of macrophages towards the antitumor M1 phenotype, thereby inhibiting glioma growth.

Objective:To design a knowledge-based cervical cancer planning model and apply it to cases of endometrial cancer and rectal cancer in order to explore the generalization of the model.Methods:A total of 179 cases of pelvic regions with different prescribed doses of dual-arc volumetric modulated arc therapy clinical plans were collected, of which 99 cases of cervical cancer clinical plans with a prescribed dose of 50.4 Gy were used as the training set to establish the RapidPlan model, and the remaining clinical plans were divided into 4 validation groups with 20 cases in each group. The clinical plans for cervical cancer and endometrial cancer with a prescription dose of 50.4 Gy were named groups A and B, while the clinical plan for endometrial cancer and rectal cancer with a prescription dose of 45 Gy were named groups C and D. The model was used to redesign the clinical plans in the 4 groups and the automatic plans were obtained. The planning target volume (PTV) and organ at risk (OAR) dosimetry parameters were compared between automatic plans and clinical plans.Results:The conformity index (CI) of the automatic plans in the A, B, C, and D groups were equivalent to that of the clinical plans ( P>0.05). The homogeneity index (HI) and D2% of the automatic plans in groups A, B, and C were all lower than those in clinical plans(HI, Z=-3.248, -3.360, -2.329, P<0.05; D2%, Z=-2.987, -3.397, -2.442, P<0.05). The HI and D2% of the automatic plans in group D were similar those in the clinical plans ( P>0.05). While ensuring the PTV coverage, the average value of OAR dosimetry parameters in all automatic plans groups were lower than that of the clinical plans. Conclusions:The RapidPlan model established by the cervical cancer clinical plans can complete the automatic plan design for endometrial cancer and rectal cancer under different prescription doses, which preliminarily proves the possibility of the generalization of the RapidPlan model.

Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

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*