ObjectiveTo investigate the difference in bilateral lower limb muscle synergy mode during gait in patients after unilateral anterior cruciate ligament reconstruction. MethodsElectromyography from bilateral lower limb muscles during gait were collected from twelve male and eight female patients after unilateral anterior cruciate ligament reconstruction in Affiliated Hospital of Wuhan Sports University, from April to June, 2023. The data were analyzed using non-negative matrix decomposition algorithm to extract the number of muscle synergies in the affected and unaffected legs, the time to peak activation of muscle synergies and the relative weights of the muscles. ResultsSix types of muscle synergy were identified in the unaffected leg of males during gait, while five types were identified in the affected leg, lacking synergy 2 that mainly from the tibialis anterior muscle. Six types of muscle synergy were identified in both legs in females during gait. There was no significant difference in the time to peak activation of muscle synergies between both legs in males (P > 0.05). However, the time to peak activation of muscle synergies increased in females in the affected leg for synergy 3 and synergy 5 (P < 0.05). The relative weight of the rectus femoris was lower in synergy 1 in the affected leg in males (P < 0.05). For female, the relative weight of the vastus lateralis was higher and the relative weight of the biceps femoris was lower in synergy 2 in the affected leg in females (P < 0.05); while the relative weight of the rectus femoris was lower in synergy 3 (P < 0.05), and the relative weight of the biceps femoris was lower in synergy 6 (P < 0.05). ConclusionMales would freeze the muscle synergy dominating ankle dorsiflexion in affected leg to enhance ankle stability, and reduce the relative weight of rectus femoris during the loading response phase to weaken the knee landing cushioning. However, females would delay the activation of synergies dominating in loading response phase and the mid-stance phase, enhance the relative weight of vastus lateralis during the loading response phase, and reduce the relative weights of rectus femoris in the loading response phase and the relative weight of biceps femoris in the mid-stance phase, to limit knee flexion.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

To investigate the degrees of EB virus reactivation in patients with inflammatory bowel disease (IBD) treated with different biologics and the levels of important cytokines associated with relapse under the influence of this virus, and to assess its diagnostic efficacy as a risk factor for identifying disease relapse. A case-control retrospective study based on patients′ hospitalization history data was conducted to select a total of 105 patients who were hospitalized in the Department of Gastroenterology, Huashan Hospital, Fudan University, with a confirmed diagnosis of IBD from 2021 to 2023. Based on the quantitative copy level of whole blood EBV DNA to determine the status of EB virus infection in patients, integrated cytokine 8 (IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ), C-reactive protein, and fecal calreticulin, to find the risk variable associated with treatment relapse. Logistic regression was used to analyze the relative risk between this variable and treatment relapse, and ROC curves were used to predict the diagnostic efficacy of cytokine multifactorial thresholds for treatment relapse. Results showed that the median age of the study was 37(26, 54)years, with a minimum of 18 years and a maximum of 70 years, with a median age of 34(24, 51) years for Crohn′s Disease (CD) patients and 46(35, 60) years for Ulcerative colitis (UC) patients, with a statistically difference between the ages of the two groups ( t=2.675, P=0.009). The median age at 50 years of patients treated with Vedolizumab (VDZ) in the UC group was higher than in the treatment groups other than VDZ. The highest rate of EB virusreactivation was found in the group treated with immunosuppressants Azathioprine (AZA) combined with anti-tumor necrosis factor-α (anti-TNF-α) and VDZ (62.5% in both groups), and the lowest in the group treated with Ustekinumab (UST) (0%). IL-2 levels were elevated in the AZA+anti-TNF-α and anti-TNF-α groups after EB virus entryreactivation. Three treatment groups, AZA+anti-TNF-α, anti-TNF-α, and VDZ, had elevated levels of IL-6 expression after EB virus entry reactivation.In the anti-TNF-α treatment-related group IL-2was associated with treatment relapse in IBD ( OR=1.127, 95% CI: 1.044-1.256, P=0.007). ROC analysis showed that the AUC for IL-2 combined with EB virus in a replicative state was 0.8282 ( P=0.006), with a negative predictive value and a positive value of 90% and 75%, respectively. As well as IL-6 was associated with treatment relapse of IBD in the anti-TNF-αtreatment-related group as well as in the VDZ-treated group ( OR=1.049, 95% CI: 1.017-1.095, P=0.008). ROC analysis showed that the diagnostic sensitivity and specificity for post-treatment relapse at a critical value of 6.10 pg/ml for IL-6 was 83.33% and 82.93%, respectively. The AUC for IL-6 combined with EB virus in a replicative state was 0.900 ( P<0.000 1), with negative and positive predictive value of 84.09% and 73.33%, respectively. In summary, the imbalance of proinflammatory and anti-inflammatory cytokines varies between drugs, with EBV in a replication-activated state, combined with elevated levels of IL-2 as well as IL-6 expression being a risk factor for relapse in patients treated with anti-TNF-α-related drugs and VDZ.

To investigate the degrees of EB virus reactivation in patients with inflammatory bowel disease (IBD) treated with different biologics and the levels of important cytokines associated with relapse under the influence of this virus, and to assess its diagnostic efficacy as a risk factor for identifying disease relapse. A case-control retrospective study based on patients′ hospitalization history data was conducted to select a total of 105 patients who were hospitalized in the Department of Gastroenterology, Huashan Hospital, Fudan University, with a confirmed diagnosis of IBD from 2021 to 2023. Based on the quantitative copy level of whole blood EBV DNA to determine the status of EB virus infection in patients, integrated cytokine 8 (IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ), C-reactive protein, and fecal calreticulin, to find the risk variable associated with treatment relapse. Logistic regression was used to analyze the relative risk between this variable and treatment relapse, and ROC curves were used to predict the diagnostic efficacy of cytokine multifactorial thresholds for treatment relapse. Results showed that the median age of the study was 37(26, 54)years, with a minimum of 18 years and a maximum of 70 years, with a median age of 34(24, 51) years for Crohn′s Disease (CD) patients and 46(35, 60) years for Ulcerative colitis (UC) patients, with a statistically difference between the ages of the two groups ( t=2.675, P=0.009). The median age at 50 years of patients treated with Vedolizumab (VDZ) in the UC group was higher than in the treatment groups other than VDZ. The highest rate of EB virusreactivation was found in the group treated with immunosuppressants Azathioprine (AZA) combined with anti-tumor necrosis factor-α (anti-TNF-α) and VDZ (62.5% in both groups), and the lowest in the group treated with Ustekinumab (UST) (0%). IL-2 levels were elevated in the AZA+anti-TNF-α and anti-TNF-α groups after EB virus entryreactivation. Three treatment groups, AZA+anti-TNF-α, anti-TNF-α, and VDZ, had elevated levels of IL-6 expression after EB virus entry reactivation.In the anti-TNF-α treatment-related group IL-2was associated with treatment relapse in IBD ( OR=1.127, 95% CI: 1.044-1.256, P=0.007). ROC analysis showed that the AUC for IL-2 combined with EB virus in a replicative state was 0.8282 ( P=0.006), with a negative predictive value and a positive value of 90% and 75%, respectively. As well as IL-6 was associated with treatment relapse of IBD in the anti-TNF-αtreatment-related group as well as in the VDZ-treated group ( OR=1.049, 95% CI: 1.017-1.095, P=0.008). ROC analysis showed that the diagnostic sensitivity and specificity for post-treatment relapse at a critical value of 6.10 pg/ml for IL-6 was 83.33% and 82.93%, respectively. The AUC for IL-6 combined with EB virus in a replicative state was 0.900 ( P<0.000 1), with negative and positive predictive value of 84.09% and 73.33%, respectively. In summary, the imbalance of proinflammatory and anti-inflammatory cytokines varies between drugs, with EBV in a replication-activated state, combined with elevated levels of IL-2 as well as IL-6 expression being a risk factor for relapse in patients treated with anti-TNF-α-related drugs and VDZ.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

Tumor heterogeneity is one of the important characteristics of melanoma. Single-cell RNA sequencing not only can further reveal the heterogeneity of melanoma cells, but also has unique advantages in analyzing the occurrence and development of melanoma, finding new targets for immunotherapy and uncovering mechanisms of drug resistance. This review summarizes the application of single-cell RNA sequencing in melanoma research.

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

[This corrects the article DOI: 10.1016/j.apsb.2020.05.004.].

OBJECTIVE To investigate the effects of different doses of dexmedetomidine on intracranial pressure in patients undergoing gynecological laparoscopic surgery. METHODS Ninety patients undergoing selective gynecological laparoscopic surgery in trendelenburg position were divided into low-dose experimental group （group D 1），high-dose experimental group （group D 2） and control group （group C ）according to random number table ，with 30 cases in each group. Group D 1 and group D 2 received continuous intravenous infusion of dexmedetomidine 1.0 μ g/kg for 10 min for induction of anesthesia ，and then continued intravenous infusion at the rate of 0.4 μg（/ kg·h）and 0.6 μg（/ kg·h）respectively. Group C was continuously pumped with the constant volume of Sodium chloride injection. Three groups stopped pumping 30 minutes before the end of the operation. The heart rate（HR）and mean arterial pressure （MAP）were recorded when entering the room （T0），10 min after intravenous pump of dexmedetomidine（T1），10 min（T2），30 min（T3），60 min（T4）after pneumoperitoneum ，10 min after pneumoperitoneum was closed to restore the supine position （T5）. At the same time ，optic nerve sheath diameter （ONSD）in both eyes was measured by ultrasound，and the occurrence of intraoperative bradycardia and the use of atropine were recorded. RESULTS There was no statistical significance in ONSD ，HR or MAP among 3 groups at T 0（P＞0.05）. Compared with T 0，ONSD of 3 groups were decreased significantly at T 1（except for group C ）；ONSD of 3 groups were increased significantly at T 2-T5，while MAP and HR were all decreased significantly （P＜0.05）. HR of group D 2 was decreased significantly at T 1（P＜0.05）. Compared with group C ， ONSD and HR of group D 1 and D 2 were all decreased significantly at T 1-T5（P＜0.05）. Compared with group C ，the number of patients with bradycardia and those who used atropine in group D 1 and D 2 were increased significantly （P＜0.05）. CONCLUSIONS Continuous pumping of dexmedetomidine during gynecologic laparoscopic surgery can reduce the increase of intracranial pressure in patients ；compared with pumping rate of 0.6 μg（/ kg·h），the change of patient ’s HR tends to be more stable with a pumping rate of 0.4 μg（/ kg·h）.