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.

ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

ObjectiveThis study aims to investigate the effects of different sizes of seedlings and melatonin treatment on physiological and biochemical indicators and bolting-related gene expression in Angelica sinensis， find substances related to early bolting， and elucidate the inhibitory mechanism of melatonin on bolting. MethodsSpectrophotometry was used to detect the related enzyme activities of A. sinensis leaves. The contents of endogenous hormones and polyamines were detected using ultra-high performance liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction （Real-time PCR） was used to detect the expression levels of bolting-related genes. Inter-group differential indicator analysis， orthogonal partial least squares discriminant analysis， and principal component analysis were comprehensively applied to identify factors related to early bolting. ResultsEndogenous jasmonic acid and melatonin were identified as the most important factors affecting early bolting. Secondly， the activity of antioxidant enzymes， abscisic acid content， gibberellin content， and the expression levels of CO3， HD3A， and FD genes had important effects on the bolting process. Compared with small seedlings， exogenous melatonin treatment mainly inhibited early bolting by increasing endogenous melatonin content， reducing gibberellin content， and decreasing the expression levels of SOC1 and FD genes. ConclusionExogenous melatonin can inhibit early bolting in A. sinensis by regulating its physiological， biochemical， and gene expression levels.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

Objective To establish a method for simultaneous determination of 11 components of Solanum nigrum from different producing areas,and to evaluate the quality by chemometrics and entropy weight-technique for order preference by similarity to ideal solution(EW-TOPSIS).Methods The 17 batches of Solanum nigrum samples from 8 provinces were collected.The high performance liquid chromatography(HPLC)method was used to simultaneously determine the contents of medioresino,pinoresinol,quercetin,rutoside,solasonine,solamargine,khasianine,solasodine,desgalactotigonin,diosgenin and β-sitosterol,and the multi-components quantitative control mode of Solanum nigrum was established.The quality evaluation model of Solanum nigrum was established by using chemical recognition pattern and EW-TOPSIS method,and the overall quality was evaluated comprehensively.Results When the 11 components were in the 0.78-39.00,0.55-27.50,0.34-17.00,0.21-10.50,41.87-2 093.50,60.95-3 047.50,2.58-129.00,1.02-51.00,0.46-23.00,1.05-52.50 and 0.42-21.00 μg/mL(r＞0.999 0),their linear relationships were good.The average recovery was 96.81％-100.28％with the RSD＜2.0％(n=9).17 batches of samples clustered into 3 categories.Solamargine,solasonine,desgalactotigonin and medioresino may be the main potential markers affecting the quality of Solanum nigrum.The results of EW-TOPSIS method showed that,the quality evaluation closeness of 17 batches of Solanum nigrum were 0.433 6,0.416 8,0.624 2,0.500 8,0.479 1,0.636 1,0.568 3,0.250 0,0.190 9,0.222 1,0.170 7,0.720 0,0.698 3,0.744 7,0.717 9,0.720 9 and 0.718 3,respectively,indicating that the overall quality of Solanum nigrum from Liaoning,Jilin and Heilongjiang were better,followed by Jiangsu,Henan and Anhui.Conclusion The established HPLC method for simultaneous determination of 11 components in Solanum nigrum is convenient and accurate.Chemometrics and EW-TOPSIS method are objective and comprehensive,which can be used for the overall quality evaluation of Solanum nigrum.

Objective To investigate the role and action mechanism of rosemarinic acid(RA)on the malignant behavior of colorectal cancer(CRC)SW480 cells.Methods We collected tumor tissues from patients with primary untreated CRC who underwent surgery in People's Hospital of Rugao from January 2019 to December 2020,as well as colon tissues from normal individuals.The expression of β-catenin was detected by immunohistochemistry and Western blotting to analyze its relationship with the clinical stage,prognosis,and immune infiltration.CCK-8 was used to detect the effects of 10,15 and 20 μmol/L of RA on the proliferation of SW480 cells;flow cytometry detected apoptosis;Transwell and scratch assay detected changes in the invasion and migration ability of the cells,respectively.Western blotting detected the expressions of proteins related to apoptosis,epithelial-mesenchymal transition(EMT),and Wnt/β-catenin pathway.A mouse model of CRC transplant tumor was established,and the effect of RA on the growth of transplant tumor was investigated by gavage administration.The levels of inflammatory factors were detected by ELISA.Results The expression of β-catenin was low in normal colon tissues and significantly higher in CRC tissues.In the CRC patients with high expression of β-catenin,the number of patients with tumors larger than 5 cm was significantly higher than that in the low expression group,whereas the overall survival of the patients was significantly smaller than that in the low expression group(P＜0.05).Cell proliferation was significantly inhibited and decreased in a concentration-dependent manner in the RA group at all concentrations(P＜0.05).In animal experiments,the expression of apoptotic proteins Bax and Bad was significantly increased and the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the RA-treated group compared with the control group(P＜0.05).It was also found that the invasive and migratory ability of SW480 cells was significantly inhibited(P＜0.05),the expression of E-cadherin protein was significantly increased,the expression of Snail,N-cadherin and Vimentin was significantly reduced(P＜0.05),the expression of Axin and GSK-3β was increased,and the expression of β-catenin was reduced(P＜0.05).Conclusion RA may inhibit the biological activity of SW480 by interfering with Wnt/β-catenin pathway-mediated EMT.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

[Objective] To investigate the inhibitory effect of quercetin on cisplatin-resistant human colorectal cancer (CRC) cells SW480 and SW620 and its possible mechanism. [Methods] Cisplatin-resistant subtypes of SW480 and SW620 cells were first cultured and the effects of quercetin on cell proliferation and chemosensitivity were determined by MTT assay. Flow cytometry was used to detect apoptosis and protein blotting was used to detect the expressions of relevant proteins. [Results] MTT assay showed that quercetin at the concentrations of 80 μmol/L and 160 μmol/L significantly inhibited the proliferation of SW480 and SW620 cells. Flow cytometry results showed that the apoptosis rate was significantly higher in the cisplatin combined with quercetin group than in the other three groups. Protein blotting showed that cleaved-caspase-3 and caspase-9 expressions were significantly increased in the cisplatin combined with quercetin group. The chemotherapeutic drug sensitivity assay showed that the elevated IC50 of drug-resistant cells was decreased significantly after quercetin administration (P<0.05). [Conclusion] The present study clarifies that quercetin can increase the sensitivity of human CRC cells to cisplatin. This effect may be related to its mechanism of action in affecting cell proliferation, apoptosis and autophagy.