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.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Objective:To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS.Methods:In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI -) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results:The linear ranges of TCC and TCS were 0.5-100.0 μg/L and 1.0-100.0 μg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 μg/L, and 0.5 and 1.0 μg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 μg/L.Conclusion:QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Objective:To establish a method for the determination of two perfluorinated compounds in urine by liquid chromatography-tandem mass spectrometry.Methods:In November 2022, urine samples were extracted by acidic methanol, purified by WAX solid phase extraction column, and eluted with methanol water, then Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) was used with 1.0 mmol/L ammonium acetate solution and methanol as mobile phase. The gradient elution was carried out, the detection was carried out by electrospray negative ion multiple response monitoring (MRM) mode, and the quantitative method was internal standard method.Results:Perfluorooctanoic acid and perfluorooctane sulfonic acid had a good linear relationship in the concentration range of 0.5-50.0 μg/L, and the correlation coefficient was >0.999. The limit of detection was 0.017 μg/L, and the limit of quantitation was 0.005 μg/L. The average recoveries were 96.3% and 101.8%, respectively. Days of precision were 3.5%-6.2% and 3.1%-7.4%, respectively, daytime precision were 4.3%-6.8% and 4.7%-8.1%, respectively.Conclusion:The established method of liquid chromatography-tandem mass spectrometry is high sensitivity and accuracy, and is suitable for the determination of perfluorooctanoic acid and perfluorooctane sulfonic acid in human urine.

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.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Objective:To explore the changes in the functional connectivity (FC) of hippocampal subregions in nicotine addicts after repetitive transcranial magnetic stimulation (rTMS) using resting-state FC.Methods:This study was a cross-sectional study. The clinical and imaging data from 20 male nicotine addicts at Zhejiang Hospital between 2022 and 2024 were analyzed prospectively. All participants received rTMS treatment and were assessed with nicotine-related clinical scales and resting-state FC analysis before and after treatment. The clinical scale evaluations included the Fagerstr?m test for nicotine dependence (FTND), smoking severity index, Minnesota nicotine withdrawal scale (MNWS), short tobacco craving questionnaire (sTCQ), and visual analog scale (VAS). Paired t-tests and Wilcoxon signed-rank tests were used to compare the differences in clinical scale scores before and after treatment. Ten subregions of the bilateral hippocampus (including the hippocampus, dentate gyrus, entorhinal cortex, hippocampus-amygdala transition area, and subiculum) were used as seed points, and paired t-tests were conducted to compare the FC differences in these subregions before and after treatment. Pearson and Spearman correlation analyses were used to assess the correlation between changes in resting-state FC in the rTMS group and clinical scale scores. Results:Compared to pre-treatment, the scores on the FTND, smoking severity index, MNWS, sTCQ, and VAS all significantly decreased after rTMS treatment in nicotine addicts (all P<0.05). Compared to pre-treatment, post-treatment FC was reduced between the left dentate gyrus subregion and the bilateral supplementary motor area and left middle cingulate gyrus, while it increased between the left entorhinal cortex subregion and the right middle and superior temporal gyri, and between the left hippocampus-amygdala transition area subregion and the bilateral calcarine cortex and cuneus (Gaussian random field correction, voxel-level P<0.01, cluster-level P<0.05). Negative correlations were observed between the FC difference in the left hippocampus-amygdala transition area subregion and the right calcarine cortex and the difference in sTCQ-impulse score before and after treatment ( r=-0.447, P=0.048). Negative correlations were observed between the FC difference in the left hippocampus-amygdala transition area subregion and the right cuneus and the difference in the sTCQ-expectation score ( r=-0.559, P=0.010). Negative correlations were observed between the FC difference in the left hippocampus-amygdala transition area subregion and the left calcarine cortex and the differences in sTCQ-emotion and sTCQ-expectation scores ( r=-0.516, P=0.020; r=-0.466, P=0.038, respectively). Negative correlations were observed between the FC difference in the left hippocampus-amygdala transition area subregion and the left cuneus and the differences in sTCQ-emotion and sTCQ-expectation scores ( r=-0.459, P=0.042; r=-0.501, P=0.024, respectively). Conclusion:Changes in FC in certain hippocampal regions are observed in nicotine addicts following rTMS treatment, suggesting that hippocampal subregions may serve as potential biomarkers for nicotine addiction withdrawal to some extent.

Objective To develop exercise programs for patients with total hip replacement at different stages in order to promote postoperative rehabilitation and functional recovery.Methods According to the"6S"evidence pyramid model,using computer,a systematic search was conducted using computer-based top-down methods across BMJ Best Practice,Up To Date,the Joanna Briggs Institute evidence-based practice database(JBI),the Centre for Evidence-Based Healthcare,the National Institute for Health and Care Excellence(NICE)website,the Guidelines International Network(GIN),the National Guideline Clearinghouse(NGC),the Scottish Intercollegiate Guidelines Network(SIGN),Medlive,Cochrane Library,Embase,PubMed,CINAHL,Web of Science,China National Knowledge Infrastructure(CNKI),China Biomedical Literature Service System,Wanfang Data Knowledge Service Platform,and VIP Database,to select literature related to exercise for patients undergoing total hip replacement.Three researchers independently assessed these documents and extracted evidence to preliminarily form exercise programs.The Delphi method was used to further validate the scientific and practical aspects of the exercise programs by two rounds of consultation.Results Specific exercise programs for patients undergoing total hip replacement were developed for the preoperative stage,postoperative 1(within 1 week after operation),postoperative stage 2(2-6 weeks after operation),and postoperative stage 3(7-12 weeks after operation),with toatal 41 items.Conclusion The exercise programs developed in this study are scientifically sound and reasonable.They can provide reference for medical staff and patients in related fields.

Objective:To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS.Methods:In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI -) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results:The linear ranges of TCC and TCS were 0.5-100.0 μg/L and 1.0-100.0 μg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 μg/L, and 0.5 and 1.0 μg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 μg/L.Conclusion:QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Objective:To establish a method for the determination of two perfluorinated compounds in urine by liquid chromatography-tandem mass spectrometry.Methods:In November 2022, urine samples were extracted by acidic methanol, purified by WAX solid phase extraction column, and eluted with methanol water, then Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) was used with 1.0 mmol/L ammonium acetate solution and methanol as mobile phase. The gradient elution was carried out, the detection was carried out by electrospray negative ion multiple response monitoring (MRM) mode, and the quantitative method was internal standard method.Results:Perfluorooctanoic acid and perfluorooctane sulfonic acid had a good linear relationship in the concentration range of 0.5-50.0 μg/L, and the correlation coefficient was >0.999. The limit of detection was 0.017 μg/L, and the limit of quantitation was 0.005 μg/L. The average recoveries were 96.3% and 101.8%, respectively. Days of precision were 3.5%-6.2% and 3.1%-7.4%, respectively, daytime precision were 4.3%-6.8% and 4.7%-8.1%, respectively.Conclusion:The established method of liquid chromatography-tandem mass spectrometry is high sensitivity and accuracy, and is suitable for the determination of perfluorooctanoic acid and perfluorooctane sulfonic acid in human urine.