Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

The mechanism of acupuncture in treating primary dysmenorrhea(PD)in rats was reviewed.The research on the mechanism of acupuncture in the treatment of PD involves endocrine,nervous,immune,metabolic and other aspects.However,the basic research did not actively pay attention to the clinical problems encountered in the treatment of PD by acupuncture and moxibustion,including the rule of point selection and the correlation mechanism between acupoints and uterus in the treatment of PD by acupuncture and moxibustion,the key technical parameters of the treatment of PD by acupuncture and moxibustion and the rule of the action of acupuncture and moxibustion.The basic research of acupuncture treatment of primary dysmenorrhea should pay attention to translational medicine.

Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.

Objective:To investigate the value of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of extensive-stage small cell lung cancer (ES-SCLC) patients treated with the first-line atezolizumab immunotherapy and chemotherapy.Methods:From the Project Data Sphere platform, the clinical data and laboratory test data of 53 ES-SCLC patients who received the first-line atezolizumab immunotherapy and chemotherapy in the global multicenter phase Ⅱ prospective study NCT03041311 from February 2017 to February 2022 were collected. The Contal-O'Quigley method was used to calculate the optimal cut-off value of baseline dNLR for determining the overall survival (OS) of patients. The dNLR higher than or equal to the optimal cut-off value was defined as high dNLR, and less than the optimal cut-off value was defined as low dNLR. According to optimal cut-off value, the dNLR levels at baseline and after 4 cycles of chemotherapy were determined, and dynamic dNLR grouping was performed (low risk: low dNLR at baseline and after 4 cycles of chemotherapy; intermediate risk: high dNLR at baseline or after 4 cycles of chemotherapy; high risk: high dNLR at baseline and after 4 cycles of chemotherapy). The differences in clinicopathological features between the baseline high dNLR group and low dNLR group were analyzed. Kaplan-Meier method was used to draw the OS and progression-free survival (PFS) curves, and log-rank test was used to compare the differences between the two groups. Univariate Cox proportional hazards model was used to analyze the influencing factors of OS and PFS. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline dNLR grouping and dynamic dNLR grouping for 1-year OS rate in ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.Results:Among the 53 patients, 34 (64.20%) were male and 19 (35.80%) were female; 27 (50.90%) were < 65 years old and 26 (49.10%) were ≥65 years old. The optimal cut-off value of baseline dNLR for determining the OS was 1.79. There were 17 cases in low dNLR group and 36 cases in high dNLR group at baseline. The proportion of patients with elevated serum lactate dehydrogenase (LDH) in the baseline high dNLR group was higher than that in the baseline low dNLR group [58.33% (21/36) vs. 17.65% (3/17), χ2 = 7.72, P = 0.005]. The 1-year OS rates of the baseline high and low dNLR groups were 44.0% and 81.9%, and the 1-year PFS rates were 2.5% and 17.6%. The differences in OS and PFS between the two groups were statistically significant (both P < 0.05). There were 38 patients with complete dynamic dNLR data, including 9 cases of low-risk, 19 cases of medium-risk and 10 cases of high-risk, and the 1-year OS rates of the three groups were 90.0%, 67.5% and 33.3%, the difference in OS between the three groups was statistically significant ( P = 0.011). Univariate Cox regression analysis showed that baseline dNLR (low dNLR vs. high dNLR) was the influencing factor for OS of patients ( HR = 0.163, 95% CI 0.057-0.469, P = 0.001) and PFS ( HR = 0.505, 95% CI 0.268-0.952, P = 0.035). Time-dependent ROC curve analysis showed that the area under the curve (AUC) of baseline dNLR grouping and dynamic dNLR grouping for predicting 1-year OS rate of ES-SCLC patients receiving the first-line atezolizumab combined with chemotherapy was 0.674 (95% CI 0.575-0.887) and 0.731 (95% CI 0.529-0.765). Conclusions:Baseline and dynamic dNLR grouping may be effective markers for predicting the prognosis of ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.

Objective:To explore the prognostic value of pretreatment albumin in extranodal nasal type NK/T cell lymphoma (ENKTL).Methods:The clinical data of 184 ENKTL patients in Shanxi Province Cancer Hospital from January 2002 to December 2018 were retrospectively analyzed. The Contal-O'Quigley change point method was used to determine the optimal cut-off value of albumin for predicting the prognosis of patients. The propensity score matching (PSM) was used to minimize selection biases. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards model was used to determine the factors affecting survival. The time-dependent receiver operating characteristic curve, Akaike information criterion and integrated Brier score were used to evaluate the efficacy of international prognostic index (IPI), Korean prognostic index (KPI) and prognostic index of NK cell lymphoma (PINK) models incorporating albumin for predicting the prognosis of patients.Results:The optimal cut-off value of pretreatment albumin for predicting the prognosis of ENKTL patients was 37.5 g/L. The 3-year and 5-year overall survival (OS) rates in >37.5 g/L group (126 cases) were 66.2% and 60.3%, and the progression-free survival (PFS) rates were 58.8% and 49.6%; the 3-year and 5-year OS rates in ≤37.5 g/L group (58 cases) were 35.0% and 32.4%, and the PFS rates were 32.5% and 30.0%. The OS and PFS in > 37.5 g/L group were better than those in ≤37.5 g/L group (both P<0.001). After PSM, the OS and PFS in >37.5 g/L group were still better than those in ≤37.5 g/L group (both P = 0.002). Multivariate analysis showed that albumin was an independent influencing factor for OS ( RR = 0.419, 95% CI 0.266-0.660, P < 0.001) and PFS ( RR = 0.493, 95% CI 0.322-0.755, P < 0.001). After PSM, albumin was still an independent influencing factor for OS ( RR = 0.305, 95% CI 0.156-0.598, P = 0.001) and PFS ( RR = 0.341, 95% CI 0.185-0.627, P = 0.001). The prognostic prediction performance of the IPI, KPI and PINK models incorporating albumin were all improved. Conclusions:Pretreatment albumin is an important prognostic indicator for ENKTL.

Objective:To compare the efficacy and safety of Tonghua Dongbao′s insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes.Methods:A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment.Results:For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P=0.320). Ratios of negative to positive were 7.43% and 10.61% ( P=0.360), and ratios of positive to negative were 10.40% and 7.58% ( P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P=0.371), and the incidence of adverse events was 76.60% and 77.70% ( P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions:Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Objective:To investigate the clinical characteristics of pregnant women with leukemia, the condition of leukemia and the influence of clinical treatment on maternal and infant outcomes, and to explore the best clinical management method of leukemia in pregnancy.Methods:Among 79 890 pregnant and lying-in women in Qilu Hospital of Shandong University from January 2004 to December 2015, 22 cases (0.028%) were with leukemia, including 5 cases of leukemia diagnosed before pregnancy [all acute myeloid leukemia (AML)] and 17 cases of leukemia diagnosed for the first time after pregnancy [9 cases of AML, 5 cases of chronic myeloid leukemia (CML), 2 cases of acute lymphoblastic leukemia (ALL), and 1 case of chronic lymphocytic leukemia (CLL)]. According to the gestational weeks of admission and confirmed gestational weeks of leukemia, the 22 patients were divided into early-stage group (initial gestational week < 14 weeks, 5 cases), mid-stage group (newly diagnosed gestational week ≥ 14 weeks and < 28 weeks, 11 cases), and late-stage group (newly diagnosed gestational week ≥ 28 weeks, 6 cases, including 2 cases with previous diagnosis of leukemia). The final pregnancy outcomes included abortion, induced labor, premature delivery, full-term delivery and maternal and infant death. The effects of clinical treatment and obstetric treatment of leukemia on the final maternal and infant outcomes, follow-up to understand the progress of primary disease and fertility of pregnant women, and the impact of leukemia and pregnancy treatment on long-term health status of infants were analyzed.Results:Among 22 patients with leukemia in pregnancy, 14 cases (63.6%) (5 cases in early-stage group and 9 cases in mid-stage group) choosed to give up pregnancy, including 4 cases of early pregnancy abortion and 10 cases of mid pregnancy induced abortion; 12 cases of 14 cases were induced abortion or induced labor after leukemia remission induced by advanced chemotherapy. The remaining 8 patients (2 cases in mid-stage group and 6 cases in late-stage group) continued pregnancy and gave birth to live infants, of which 3 cases received chemotherapy before delivery.Conclusions:Gestational leukemia is a high-risk obstetric case, but it is still expected to achieve good pregnancy outcome under good management and treatment. On the basis of following the principles of leukemia treatment, according to the gestational weeks and patients' wishes, the individualized clinical management plan is formulated, and the accurate chemotherapy timing is conducive to the prognosis of mother and infant.

Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

Objective To evaluate the clinical efficacy of intra-articular injection of ozone in collagen-induced arthritis (CIA) rats and to assess its effects on serum receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) levels. Methods Forty weight age malched Wistar rats were randomly divided into normal control group (normal group), the CIA model group (CIA group), ozone (O 3 group), and methotrexate (MTX group). In addition to the normal control group, Freund's complete adjuvant and bovine type Ⅱ collagen were injected to establish the rat model of CIA. After the model was sucessfully developed, double ankle injection concentration ozone group of 40 μg/ml of O3 each 1 ml, 1 times a week, a total of injection for 3 weeks for the experimenal group. MTX group of 0.9 mg/kg was injected 1 times a week for 3 weeks for the MTX group. Degree of foot swelling was measured, and radiographic assessment of arthritis index (AI) score was performed. One week after treatment, angular vein blood was collected for the rats after the intervention, flow multi-factor detection technology was used to test each rat. T test or Wilcoxon rank test was used to compare the difference between groups. Results ① After 3 week administration with O3, dcgree of foot swelling, and AI of the O3 group was reduced significanly than the CIA group during the same period (foot swelling degree: O3 group: (4.21±0.14) ml, CIA group (9.12±0.17) ml, T=64.08, P=0.00; AI O3 group: [(2.97± 0.18) ml, CIA group: 5.76 ±0.13, T=37.24, P=0.00], and X-ray showed joint damage was alleviated. ② The serum level of RANKL in the CIA group was significantly higher than of the normal group [CIA model group 1890.70(797.03, 10571.94)], normal group [74.46(29.21, 95.37), T=43, P=0.005] during the same period; The serum level of RANKL in the O3 group was significantly lower than the CIA group [O3 group 28.09 (14.11, 207.30), CIA group 1890.70 (797.03, 10571.94), T=39, P<0.05]; RANKL level of the Ozone group when compared with MTX group, was not statistically significantly difference (T=52, P>0.05).③Serum RANKL/OPG of the CIA group was significantly higher than that of the normal group during this period, the difference was statistically significant [CIA group 250.68(42.33, 2959.78), normal group 4.32(3.16,5.30), T=36, P<0.01);The serum level of RANKL/OPG in the O3 group was significantly lower than the CIA group [O3 treatment group 5.10 (3.38, 6.64), CIA group 250.68 (42,33, 2959.78), T=36, P<0.01]; There was no statistically significant difference of the serum RANKL/OPG between the O3 group and the MTX group (T=62.5, P>0.05). Conclusion Intra-articular injection of concentration of 40 μg/ml of O3 can reduce RA rat joint swelling degree, which may relate to the mechanism that O3 can lower levels of serum RANKL and RANKL/OPG ratio, reduce osteoclast formation and activation.

Objective To observe the effects of intra-articular ozone injection on the secretion of tumor necrosis factor (TNF)-α,Interleukin (IL)-6,IL-17A,and vascular endothelial growth factor (VEGF) in the serum of rats with collagen-induced arthritis (CIA) and explore the therapeutic mechanism of ozone in RA treatment.Methods Thrity-two Wistar rats were randomized into 4 groups,including the ozone groups that receivedintra-articularinjection of 40 μg/ml ozone (O3 group),a blank control group (normal group),a methotrexate (MTX) group (MTX group) anda collagen-induced arthritismodel (CIA group).All the rats,except for those in the blank control group,were subjected to hypodermic injection of bovine collagen Ⅱ and complete Freund's adjuvant to induce CIA.Ozone treatment was administered once weekly for 3 weeks starting at 14 days after the model were established.MTX group were treated with methotrexate 0.9 mg/kg,once a week,a total of three weeks.The swelling degree of the foot were observed,and the serum contents of TNF-oα,IL-6,IL-17A and VEGF were detected.One-way analysis of variance or Kruskal-Wallis test was used to evaluate the experimental data.Results At the end of treatment,the degree of foot swelling was reduced significantly in rats with O3 group compared with that in the CIA group [(4.21±0.14) ml vs (9.12±0.17) ml,t=8.43,P=0.023].The serum concentration of TNF-α,IL-6 and VEGF showed significant difference between the CIA group and the O3 group[91.55(86.55,98.53) pg/ml vs 14.45 (12.55,16.15) pg/ml,x2=6.216,P=0.002;145.08(37.44± 362.82) pg/ml vs 5.84(5.47,15.93) pg/ml,x2=13.136,P=0.004;51.56(46.09,74.10) pg/ml vs.36.22(32.18,41.69) pg/ml,x2=3.732,P=0.002].There was no statistically significant difference between the O3 group and MTX group [14.45(12.55,16.15) pg/ml vs [12.45(11.80,15.60) pg/ml,x2=0.243,P＞0.05;5.84(5.47,15.93) pg/ml vs 7.86(5.25,15.23) pg/ml,x2=0.058,P＞0.05;36.22(32.18±41.69) pg/ml vs 40.17(35.47,50.73) pg/ml,x2=0.516,P＞0.05].The serum concentration of IL-17A showed no significant difference between the normal group,the CIAgroup,the MTX group and the O3 group (F=1.827,P=0.165).Conclusion Intra-articular injecfion of 40 μg/ml ozone can attenuate synovitis in rats with CIA,the mechanism may relate to the inhibition of TNF-oα,IL-6 and VEGF in the serum.