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 systematically evaluate the efficacy and safety of eltrombopag combined with immunosuppressive therapy （IST） for severe aplastic anemia （SAA）， and to provide evidence-based basis for clinical treatment of SAA. METHODS Retrieved from PubMed， Embase， Cochrane Library， ClinicalTrials.gov， VIP， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about eltrombopag combined with IST （trial group） versus IST alone （control group） were collected from the inception to May 2023. After data extraction and quality evaluation （Cochrane manual 5.1.0） of included studies， meta-analysis， subgroup analysis， sensitivity analysis and publication bias analysis were performed by using RevMan 5.4 software. RESULTS A total of 12 studies were screened， including 1 344 patients. Compared with control group， objective remission rate （ORR） （RR＝1.34， 95%CI was 1.06-1.69， P＝0.01） and complete response rate （CRR） （RR＝1.88， 95%CI was 1.31-2.71， P＝ 0.000 6） at 3 months， ORR （RR＝1.33，95%CI was 1.23-1.43， P＜0.000 01） and CRR （RR＝1.88，95%CI was 1.57-2.25，P＜0.000 01） at 6 months were significantly increased in trial group. There was no statistically significant difference between the two groups in ORR （RR＝0.99， 95%CI was 0.82-1.18， P＝0.88） and CRR （RR＝1.02， 95%CI was 0.78-1.34， P＝0.87） at 12 months， two-year overall survival （OS） rate （HR＝0.61， 95%CI was 0.31-1.22， P＝0.17）， two-year event-free survival （EFS） rate （HR＝0.81， 95%CI was 0.61-1.07， P＝0.14）， clone evolution rate（RR＝1.01， 95%CI was 0.51-2.00， P＝ 0.98） or the incidence of adverse drug reactions such as liver/renal insufficiency， rash （P＞0.05）. Results of subgroup analysis showed that ORR and CRR of trial group at 6 months were higher than those of the control group in RCT and the cohort study subgroups （P＜0.05）. There was no statistically significant difference in the two-year OS rate， two-year EFS rate or clone evolution rate between trial group and control group in the two subgroups （P＞0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS The addition of eltrombopag in the IST regimen of SAA can improve the early hematological remission rate of patients， has no significant impact on short-term survival， and will not increase the occurrence of adverse drug reactions and clonal evolution.

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Platycodon ; Colon/pathology* ; Cytokines ; Anti-Inflammatory Agents/therapeutic use* ; Polysaccharides/therapeutic use* ; Dextran Sulfate ; Disease Models, Animal ; Colitis/chemically induced* ; Mice, Inbred C57BL

Objective:To explore the effect of virtual reality (VR) on sleep quality, sleep structure and neuropsychological characteristics of patients with chronic insomnia.Methods:Fifty one patients with chronic insomnia enrolled from Department of Neurology, General Hospital of Tianjin Medical University from October 2021 to April 2022 were chosen; according to their wills, they were divided into VR combined drug treatment group ( n=26) and drug treatment group ( n=25). Patients in drug treatment group accepted non-benzodiazepine combined with melatonin receptor agonist and serotonin reuptake inhibitor; in patients of VR combined drug treatment group, VR was added 30 min/d for 5 d/week on basis of above drug therapy. Subjective sleep quality was assessed by Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Scale (ISI). Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess anxiety and depression. Mini-Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT), Digital Span Test (DST), Trail Making Test (TMT), Stroop Color Word Test A/B/C, Judgment of Line Orientation Test (JLO), and Symbol Digit Modalities Test (SDMT) were used to assess the overall and individual cognitive functions. Portable sleep monitor (PSM)-100A based on cardiopulmonary coupling technology was used to evaluate the sleep structure. Differences of subjective sleep quality, sleep structure, and neuropsychological characteristics were compared between the 2 groups before and after treatment and in VR combined drug treatment group before and after treatment. Results:(1) After 6 weeks of treatment, compared with the drug treatment group, the VR combined with drug treatment group had significantly decreased scores of PSQI, ISI, HAMD and HAMA, increased total scores of AVLT immediate memory, scores of AVLT short delay recall, long delay recall and recognition, higher SDMT scores, increased correct times of DST reciting in reverse order, shorter time in TMT-A and TMT-B, higher proportion of high frequency coupled sleep (HF, stable sleep), lower proportion of low frequency coupled sleep (LF, unstable sleep), and decreased LF/HF ( P<0.05). (2) The VR combined with drug treatment group after VR treatment had significantly decreased PSQI, ISI, HAMD and HAMA scores, higher total scores of AVLT immediate memory, higher scores of AVLT short delay recall, long delay recall and recognition, shorter time in TMT-A and TMT-B, increased correct times of DST reciting in order and reciting in reverse order, and higher scores of JLO, Stroop Color Word Test A/B/C and SDMT, higher proportion of HF sleep, lower LF sleep, decreased LF/HF, and decreased arousal frequency compared with that before VR treatment ( P<0.05). Conclusion:VR combined with drug treatment can effectively improve the subjective sleep quality and sleep structure, reduce depression and anxiety, and improve memory and attention of patients with chronic insomnia.

Objective:To analyze the characteristics of gamma oscillation in chronic insomnia patients with anxiety and depression, and to investigate its underlying neural mechanism.Methods:According to the anxiety and depression scores, the subjects with chronic insomnia who met the diagnostic criteria were divided into chronic insomnia with anxiety and depression group ( n=19) and chronic insomnia group ( n=13). Healthy subjects matched with age, gender, and educational background were selected as the normal control group ( n=16). The EEGs from the three groups under resting state and cognitive load state were collected.The relative gamma power was then calculated by fast Fourier transform.The spatial distribution pattern of the gamma oscillation in the three groups was analyzed.Spearman correlation analysis was employed to quantify the correlation between relative gamma powers and sleep scale, anxiety and depression scale scores. Results:In the resting state, the relative gamma power in the chronic insomnia with anxiety and depression, chronic insomnia and normal control group was 0.192 1±0.008 0, 0.210 3±0.009 6, 0.237 3±0.006 4, respectively.In the cognitive load state, the relative gamma power in the three groups increased compared with those in the resting state (0.220 7±0.008 1, 0.249 5±0.009 8, 0.267 7±0.007 2, respectively) (all P<0.05). In the resting state, the relative gamma power (F3, F4, C3, C4, P3, P4, O2, F8, T4) in the chronic insomnia with anxiety and depression group (0.179 9±0.009 7) and the chronic insomnia group (0.194 4±0.010 4) was lower than that in control (0.236 0±0.012 0, P<0.05). In the cognitive load state, the relative gamma power (F3, C3, C4, P3, P4, T4) in the chronic insomnia with anxiety and depression group (0.207 3±0.009 7) was lower than that in control (0.259 1±0.009 4)( P<0.05). There was a significant negative correlation between the relative gamma power in the nodes(F3, C3, P3)and the insomnia, anxiety and depression in the three groups(correlation coefficient r=-0.467--0.274, P<0.05). Conclusion:Chronic insomnia patients with anxiety and depression are often accompanied by cognitive dysfunction.The loss of gamma oscillation in left posterior, left central and left apex may be one of the potential neural mechanisms of cognitive dysfunction in chronic insomnia patients with anxiety and depression.

Objective To evaluate the effectiveness of swallowing training supplemented with neuromuscular electrical stimulation to provide a reference for clinical treatment and further study.Methods Reports of randomized and controlled trials of surface neuromuscular electrical stimulation in treating post-stroke dysphagia were sought in the Cochrane library,the PubMed and Embase databases,the Cumulative Index to Nursing and Allied Health Literature (CINAHL),and also in the ProQuest,PsycARTICLES,CBMdisc,China National Knowledge Infrastructure (CNKI),CQVIP database and Wanfang databases.All of the literature found was evaluated by 2 researchers according to predefined inclusion and exclusion criteria and the data were extracted and combined.Then meta-analysis was performed using version 5.3 of the RevMan software package.Results Eleven randomized and controlled trials involving 576 patients were included in the meta-analysis.Together,the data showed that swallowing training supplemented by neuromuscular electrical stimulation is significantly more effective than swallowing training alone in improving swallowing function.It reduces the risk of aspiration and improves quality of life.It does not,however,generally shorten the pharyngeal transmit time.Conclusions Swallowing training supplemented with neuromuscular electrical stimulation is a promising approach for treatment of post-stroke dysphagia and warrants further study.

Objective To validate the analytical performance of a cardiac troponin I(cTnI)assay AccuTnI+3 on chemiluminescnet analyzer DXI800 and Access2;and to establish the 99th percentile of cTnI in an apparently healthy Chinese population.Methods The subjects are composed of 1 369 apparently healthy people and 20 acute myocardial infarction(AMI)patients from Wuhan Asian Heart Hospital and Fuwai Hospital from October 2014 to June 2015.The healthy people include 680 males and 689 females;with 340 subjects aged 18-30,674 subjects aged 31-64, and 355 subjects aged ≥65.The detection limits and imprecision of AccuTnI +3 assays were validated according to CLSI EP 15-A2 and EP17-A2 documents;the same samples were analyzed on DXI800 and Access2 to assess the consistency between the two analyzers using Bland Altman plot and Passing-Bablok regression.The correlation between different sample types (lithium heparin plasma, EDTA plasma & serum)were assessed using linear regression analysis.The lithium heparin plasmasamples from 1 369 apparently healthy people were analyzed to calculate the 99th percentile of cTnI.The cTnI concentrations were compared among age and sex groups.The 99th percentile of cTnI were also calculated for each group.The detection rate of cTnI in apparently healthy people was calculated using SPSS23.0.Results The limit of blank(LoB), limit of detection(LoD), and limit of quantification(LoQ)where CV%=10% were 0.007 ng/ml,0.010 ng/ml and 0.016 ng/ml on DXI800;0.008 ng/ml,0.012 ng/ml and 0.026 ng/ml on Access2,respectively.The cTnI measurements on DXI800 and Access2 were consistent and comparable.The cTnI concentrations of lithium heparin plasma, EDTA plasma and serum samples were linearly correlated pairwise: EDTA plasma measuremen t =0.76 heparin plasma measurement, R2=0.999(n=40, P<0.001); serum measuremen t =1.05 heparin plasma measurement,R2=0.996(n=40,P<0.001); serum measuremen t=1.38 EDTA plasma measurement, R2=0.993(n=40,P<0.001).The 99th percentiles were 0.030 ng/ml and 0.035 ng/ml on DXI800 and Access2,respectively,from 1 369 apparently healthy Chinese people.cTnI is significantly higher in elder group than in younger group.The 99th percentiles in 18-30 years old group,31-64 years old group,and≥65 years old group are:0.011 ng/ml,0.029 ng/ml,and 0.035 ng/ml respectively for DXI800;0.023 ng/ml,0.034 ng/ml, and 0.045 ng/ml respectively for Access2.cTnI is significantly higher in men than in women.The 99th percentiles in men and women are: 0.034 ng/ml and 0.032 ng/ml respectively for DXI800;0.043 ng/ml and 0.031 ng/ml respectively for Access2.cTnI was measurable in 62%and 87%of healthy subjects on DXI800 and Access2 systems,respectively.Conclusions The analytical performance of AccuTnI+3 assay fulfills the need of clinical use and the criteria of high-sensitive cardiac troponin assay.

Objective To study the effect and safety of modified Valdivia position and prone position in percutaneous nephrolithotomy(PCNL) on renal calculi.Methods The clinical data of 94 patients with solitary renal calculi admitted in our hospital from September 2015 to November 2016 were enrolled to this study,who were divided into control group and study group by surgery methods and body position,47 cases in each group.The control group received PCNL with prone position,and the study group were treated by PCNL with modified Valdivia position.The operative condition,postoperative condition,stone clearance rate and incidence of adverse reactions between the two groups between two groups were compared,and the levels of diastolic blood pressure(DBP),systolic blood pressure(SBP) and heart rate(HR) between the two groups were observed.Results After position placement,DBP and SBP level decreased in both groups,the level of DBP and SBP in study group were lower than the control group,the difference was significant(P<0.01).There was no significant difference in the level of HR between two groups(P>0.05).The operative time,intraoperative blood loss,hospitalization time,reoperation rate and blood transfusion rate in the study group were lower than those in control group,the differences were significant(P<0.05),the removal rate of stones was significantly higher than that of control group(χ2=9.55,P=0.00).The rate of chest stuffy and dysphoria in the study group were higher than those in control group(P<0.05).The incidence of infection,hemorrhage,pleural injury and renal injury were slightly lower than those of the control group,but there was no significant difference between two groups(P>0.05).Conclusion PCNL with modified Valdivia position has high safety and significant effect on patients with kidney stones,which can effectively remove stones,reduce operation time.