The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways,and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years,more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells,as well as the role of ferroptosis-related factors,non-coding RNA regulation,N6-methyladenosine(m6A),amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer,with a view to provide new strategies for the treatment of bladder cancer.

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.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Object:To explore the clinical effect of periacetabular osteotomy (PAO) in the treatment of developmental dysplasia of hip (DDH).Methods:The clinical data of 305 patients with DDH admitted to Tangshan Second Hospital from January 2012 to June 2018 were analyzed retrospectively. All patients were treated with PAO alone. There were 123 cases of left hip dysplasia, 131 cases of right hip dysplasia and 51 cases of double hip dysplasia (356 hips in total). The patients underwent X-ray examination before and on the second day after operation to compare the acetabular index and the lateral center edge angle (LCEA) and the anterior center edge angle (ACEA) of the acetabulum before and after operation. The ability of daily living and hip joint function were evaluated before and 6 months after operation, and Barthel index and Harris score of hip joint were compared before and after treatment. The measurement data with normal distribution are expressed in xˉ± s, and the paired t test was used for comparison before and after operation. The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison before and after surgery is performed by the rank sum test. Results:On the second day after operation, the LCEA and ACEA of 356 hip joints in 305 patients were greater than those before operation (32.5(20.0,47.5)° vs 8.5(-18.5 23.0)°, 29.0(18.5,52.3)° vs 2.5(-20.8, 24.5)°), while the acetabulum index was lower than that before operation (6.7(-8.4,12.5)° vs 26.8(10.0, 62.3)°), and the differences were statistically significant ( Z values were 51.50, 45.37, 32.22, all P<0.001). After 6 months of follow-up, the Barthel score and Harris score of the hip joint were higher than those before the operation (92.5±1.3) scores vs (65.6±1.5) scores, (96.4±2.5) scores vs (85.1±1.3) scores, and the difference was statistically significant ( t values were 335.56 and 89.70, both P<0.001). Conclusions:PAO can make the acetabulum cover the femoral head well through acetabular transposition, improve the ability of daily living and hip joint function of DDH patients, reduce pain, increase joint range of motion, and correct limb deformities. It is an effective means to treat DDH.

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

Objective:To investigate the normal range of exhaled nitric oxide (FeNO) in 6-18-year-old children in China, so as to provide a data base for the establishment of FeNO standards for Chinese children.Methods:A multi-center study was conducted on 5 949 children aged 6-18 (3 101 males and 2 848 females) in 16 pro-vinces of 7 administrative districts in China.According to the technical standard recommended by American Thoracic Society/European Respiratory Association, FeNO was measured, and the relationship of FeNO with the sex, age, height, weight, body mass index and region was discussed.Results:The geometric mean FeNO value of Chinese children aged 6-18 was 14.1 ppb, and its 95% confidence interval (skewness distribution) was 1.0-38.2 ppb.The geometric mean FeNO values of children aged 6-11 and 12-18 were 13.1 ppb and 15.7 ppb, respectively, and their 95% confidence intervals (skewness distribution) were 1.0-38.1 ppb and 2.0-38.2 ppb.For children at and under 11 years old, FeNO decreased with age, with a mean decline of 1 ppb per year.The multiple linear regression results suggested that there was a significant correlation between FeNO and age for children aged 6-11, and FeNO of children aged 12-18 was significantly correlated with the gender, height, and region(all P<0.01). Conclusions:FeNO values of Chinese children and adolescents in this study are higher than those obtained by the previous study conducted from 2010 to 2012.For children aged 12-18, 16 ppb is recommended as the clinical cut-off point.For children at or under 11 years old, the influence of age on FeNO should be considered, and the cut-off point of FeNO decreases by 1 ppb as the age is reduced by one year.

Objective To investigate the distribution of chronic disease and geriatric syndrome in hospitalized elderly patients with multimorbidity by chronic disease investigation and comprehensive geriatric assessment.Methods A total of 176 patients aged ≥60 years admitted into the geriatric department in our hospital were selected,and demographic factors were collected.Their chronic diseases and geriatric syndrome were recorded.The comprehensive geriatric assessment was consummated,and the biochemical indicators for chronic disease and geriatric syndrome were detected.Results All patients suffered from two or more kinds of chronic diseases.The top three most common diseases were hypertension (112 cases),diabetes (94 cases),and respiratory diseases (73cases).The sum of chronic diseases kinds were ≥3 in 137 patients,≥4 in 78 patients,≥5 in 40 patients.The amount of chronic diseases showed an increased tendency along with ageing.Totally 175 patients had more than one geriatric syndrome,the top three most common types were frailty and prefrailty(133 cases),visual impairment (117 cases),impaired daily activities (107 cases).There were significant differences in the number of geriatric syndrome among different age groups(x2 =16.989,P ＜ 0.001).Spearman analysis showed that the number of patients with geriatric syndrome were positively correlated with age(r =0.307,P＜0.001).Conclusions The prevalence of chronic disease and geriatric syndrome is high in hospitalized elderly patients with multimorbidity,which is increased with aging.We should pay attention to the screening of chronic disease and geriatric syndrome in multimorbid elderly patients

Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.