Epilepsy is a widespread neurological disease, which can be caused by any pathological process that may affect the structure and function of the brain.It encompasses a spectrum of pathologies rather than a singular entity.Early detection and diagnosis is the key to controlling the progression of epilepsy and improving the prognosis.Magnetic resonance imaging (MRI) is a clinically recognized method for the examination of epilepsy because of its non-ionizing radiation damage and excellent soft tissue resolution and spatial resolution.With the upgrading of MRI equipment and the open application of new imaging technologies, such as multimodal MRI that integrates multiple magnetic resonance sequences, its multi-parameter imaging and high spatial resolution have completely changed the ability to detect lesions, making significant progress in understanding epilepsy from the anatomical structure, molecular level, and biochemical metabolism.This article reviews the advances in the application of multimodal MRI technology in childhood epilepsy.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.

Objective:To investigate the clinical efficacy of neoadjuvant chemo-hormonal therapy(NCHT)followed by radical prostatectomy(RP) plus extended pelvic lymphadenectomy for very-high-risk locally advanced prostate cancer.Methods:The data of 327 cases of very-high-risk locally advanced prostate cancer treated in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, The Second Hospital of Tianjin Medical University, and The Third Affiliated Hospital of Sun Yat-sen University from December 2014 to July 2019 were retrospectively analyzed. Patients were divided into two groups according to treatment regimens: the RP group (direct RP + extended pelvic lymphadenectomy 4-6 weeks after the biopsy of prostate) and the NCHT group (4-6 cycles of NCHT prior to RP). There were 171 cases in RP group and 156 cases in NCHT group, respectively. In the RP group, the median age was 67 (ranging 44-83)years. The median PSA at diagnosis was 27.24 (ranging 4.55-207.00) ng/ml. Patients’numbers of clinical T 2, T 3a, T 3b, T 4 stage were 13, 85, 57, 16, respectively, and clinical N 1, N 0 stage were 33 and 138, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 5, 35, 41, 51, 39, respectively. In the NCHT group, The median age was 67 years, ranging 46-78 years. The median PSA at diagnosis was 72.09(ranging 4.08-722.95)ng/ml. Patients’ numbers of clinical T 2, T 3a, T 3b, T 4 stage were 11, 47, 58, 40, respectively, and clinical N 1, N 0stage were 76 and 80, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 1, 11, 33, 43, 68, respectively. At baseline, the NCHT group showed higher PSA, higher ISUP grade, and more advanced clinical stage at diagnosis( P<0.05). The PSA, pathological down-staging rate, and positive surgical margin rate as well as the biochemical recurrence free survival(bRFS)were compared between the two groups. Results:After radical prostatectomy, compared with the RP group, the NCHT group had a higher proportion of patients achieving PSA<0.2 ng/ml at 6-week postoperative follow-up ( P<0.001), a higher pathologic tumor stage down-staging rate ( P<0.001), a higher ISUP down-grading rate ( P<0.001), and a lower positive surgical margins rate ( P<0.001). In addition, 10.9% of the NCHT group achieved pT 0 or minimal residual disease in postoperative pathology exams. Eighty-three patients (48.5%) in the RP group and 125 patients (80.1%) in the NCHT group achieved undetectable PSA after surgery and entered further analysis for bRFS, which showed NCHT group had significantly longer bRFS (19.46 months vs. 6.35 months). NCHT significantly reduced the risk for biochemical recurrence in locally advanced prostate cancer patients( HR=0.278, 95% CI 0.198-0.390, P<0.001). Such a reduce in risk for biochemical recurrence was seen in all subgroups( P<0.001). Conclusions:NCHT might improve surgical outcomes as well as bRFS in very-high-risk locally advanced prostate cancer patients.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

Objective:To observe the influence of the stiffness of three-dimensionally bioprinted extracellular matrix analogue on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into skin appendage cells.Methods:(1) Sodium alginate of 1 g and 4 g gelatin, 3 g sodium alginate and 8 g gelatin were mixed respectively, and the two mixtures were dissolved in 100 mL ultra-pure water respectively to prepare two sodium alginate-gelatin composite hydrogels, named 1A4G hydrogel and 3A8G hydrogel, which were used in the subsequent experiments. The morphology of the two hydrogels at room temperature, after condensation for 15-30 min at 4 ℃ (the same condensation condition below), after condensation and cross-linking with 25 g/L calcium chloride solution (the same cross-linking condition below), and after condensation and three-dimensional printing with a three-dimensional bioprinter (the same three-dimensional printer below) and cross-linking were observed respectively. Young′s modulus (stiffness) of the two kinds of hydrogels was measured by Young′s modulus tester after condensation and cross-linking ( n=3). Two kinds of hydrogels were cross-linked and freeze-dried, and their pore structure was observed by scanning electron microscope. Two hydrogels were cross-linked and freeze-dried, and the porosity was detected by anhydrous ethanol replacement method ( n=3). (2) BMSCs were isolated from femur and tibia of 20 C57BL/6 mice (no limitation with sex, born 7 days) and cultured, and the second passage of cells was used for further test. The BMSCs single cell suspension (1.0×10 7 /mL) was mixed with 1A4G hydrogel and 3A8G hydrogel respectively at 1∶9 volume ratio to prepare BMSCs-loaded 1A4G hydrogel and BMSCs-loaded 3A8G hydrogel for three-dimensional printing. One construct was printed with 1 mL cell-loaded hydrogel (the same dosage for printing below). Mesenchymal stem cells (MSCs) specific medium was added after cross-linking, and the printed constructs were divided into 1A4G group and 3A8G group according to the hydrogel. One construct of each group cultured for 7 days was tested with live/dead kit to count the live cells and dead cells in 50-fold field of view. Nine printed constructs from each of the two groups were taken, and BMSCs of nine wells (1.0×10 6 per well) cultured with 2 mL MSCs specific medium were set as two-dimensional culture group. After 1, 3, 5 day (s) of culture, three printed constructs from 1A4G group and 3A8G group respectively and three wells of cells from two-dimensional culture group were taken to detect the absorbance value in culture medium by cell counting kit 8, denoting the cell proliferation activity. (3) BMSCs-loaded 1A4G hydrogel and BMSCs-loaded 3A8G hydrogel of 10 mL respectively were prepared as in experiment (2), which were respectively mixed with 0.5 mL plantar dermis homogenate extracted from 10 C57BL/6 mice of 1 day postnatal with unknown sex, then three-dimensionally printed, cross-linked, cultured with MSCs specific medium for 3 days and then changed to sweat gland specific medium. The printed constructs were divided into 1A4G group and 3A8G group according to their hydrogel. After 7 days of culture with sweat gland specific medium, the expressions of epithelial cell surface markers cytokeratin-5 (CK5) and CK14, sweat gland cell surface markers CK18 and Na + /K + -ATPase (NKA), and hair follicle cell surface markers CK17 and alkaline phosphatase (ALP) at protein level in cells of printed constructs in the two groups were detected by immunofluorescence method. The expressions of CK5, CK14, CK18, NKA (detecting ATP1a1), CK17, and ALP at mRNA level in cells of printed constructs in the two groups were detected with real-time fluorescent quantitative reverse transcription polymerase chain reaction ( n=3). Data were statistically analyzed with independent sample t test, Fisher′s exact probability test, analysis of variance for factorial design, and Bonferroni method. Results:(1) Compared with that of 3A8G hydrogel, 1A4G hydrogel had lower viscosity and better fluidity at room temperature. Both kinds of hydrogels were gel-like after condensation, based on which, the shape of cross-linked hydrogels was uniform and regular, with three-dimensional printing and cross-linking made hrdrogels forming solid crisscross cylindrical constructs. The Young′s modulus of 1A4G hydrogel was (52±6) kPa, which was obviously lower than (218±5) kPa of 3A8G hydrogel ( t=40.470, P<0.01). The pore structure of the two hydrogels was similar, with all the cross-sections showing porous network structure. The porosity of the two hydrogels was similar ( t=0.930, P>0.05). (2) The distribution of live/dead cells between 1A4G group and 3A8G group was similar after 7 days of culture ( P>0.05), most of which were live cells. The absorbance value in culture medium of printed constructs among 1A4G group, 3A8G group, and two-dimensional culture group didn′t show statistically significant differences after 1, 3, 5 day (s) of culture ( P>0.05). Compared with that after 1 day of culture within each group, the absorbance value in culture medium of printed constructs in 1A4G group and 3A8G group was significantly increased after 3 and 5 days of culture ( P<0.05 or P<0.01), and the absorbance value in culture medium of cells in two-dimensional culture group was significantly increased after 5 days of culture ( P<0.01). Compared with that after 3 days of culture within each group, the absorbance value in culture medium of printed constructs in 1A4G group and 3A8G group and that of cells in two-dimensional culture group was significantly increased after 5 days of culture ( P<0.01). (3) After 7 days of culture with sweat gland specific medium, the CK5, CK14, CK18, NKA, CK17, and ALP were positively expressed at protein level in cells of printed constructs in the two groups. After 7 days of culture with sweat gland specific medium, the expressions of CK5, CK14, CK18, and NKA at mRNA level in cells of printed constructs were close between the two groups ( t=0.362, 0.807, 0.223, 1.356, P>0.05); the expressions of CK17 and ALP at mRNA level in cells of printed constructs in 3A8G group were 1.96±0.21 and 55.57±11.49, respectively, which were significantly higher than 1.05±0.42 and 2.01±0.27 in 1A4G group ( t=3.333, 8.074, P<0.05 or P<0.01). Conclusions:BMSCs cultured three-dimensionally in 1A4G and 3A8G hydrogels tend to differentiate into sweat gland cells, but the BMSCs cultured three-dimensionally in 3A8G hydrogel show a stronger tendency to differentiate into hair follicle cells than the cells cultured in 1A4G hydrogel. It suggests that relatively high stiffness of three-dimensionally bioprinted extracellular matrix analogue facilitates not only differentiation of BMSCs into sweat gland cells, but also their differentiation into hair follicle cells.

Objectives: To investigate the prevalence rate and clinical characteristics of familial hypercholesterolemia (FH) in Chinese patients undergoing coronary angiography due to angina-like chest pain. Methods: From March 2011 to December 2016, a total of 9 908 consecutive patients undergoing coronary angiography in Fuwai Hospital due to angina-like chest pain were enrolled. The age of enrolled patients was (56.6±11.1) years old, and 6 782 cases (68.4%) were male. The patients were divided into two groups: FH group (n=271) and non-FH group (n=9 637) according to the Dutch Lipid Clinic Network diagnostic criteria. A retrospective analyze was performed on the baseline features between the two groups including lipids levels, coronary artery disease (CAD) characteristics, and lipids-lowering treatments. Results: In the total cohort, the prevalence of definite/probable FH was 2.7% (271/9 908). The incidence of premature coronary artery disease (PCAD) (women < 60 years old, or men < 55 years old) was higher in patients with FH than that in patients without FH (70.2%(201/271) vs. 44.5% (4 287/9 637); χ²=93.738, P<0.001). Patients with FH had higher level of TC and LDL-C when compared with patients without FH ((6.74±2.48) mmol/L vs. (4.15±1.10) mmol/L; (4.53±2.39) mmol/L vs. (2.52±0.97) mmol/L; t=19.403, 22.233, P<0.001, respectively). Additionally, 84.9% (230/271) of FH patients were treated with statin at different intensities, but none of them achieved the LDL-C<2.6 mmol/L. Conclusions Chinese patients with familial hypercholesterolemia not only showed a high presence of PCAD and higher lipids levels, but also exhibited a low rate of achievement of low-density lipoprotein cholesterol targets despite statin therapy. Our results thus highlight the importance of early diagnosis and intensive treatment of FH patients.

Objective: To analyze the prevalence and clinical features of familial hypercholesterolemia (FH) in Chinese patients with myocardial infarction (MI). Method: This retrospective study recruited a total of 2 119 consecutive patients (age (56.7±10.9) years old) undergoing coronary angiography with first MI from April 2011 to December 2016. Patients were divided into 2 groups: premature MI (male<55 years old, female<60 years old) and non-premature MI. The diagnosis of FH was established according to Dutch Lipid Clinic Network (DLCN) diagnostic criteria and referred as definite/probable FH in our study. The prevalence and clinical features of FH, including lipid level, MI characteristics and stain therapy, were explored. Multivariable logistic regression analysis was used to assess the predictive value of FH for the presence of premature MI. Results: The prevalence of definite/probable FH was 3.68% (78/2 119) in MI patients and 7.28% (68/934) in premature MI patients. Onset of MI occurred 10 years earlier in patients with definite/probable FH than those without FH ((47.9±9.4) years vs. (58.8±10.7) years, P<0.01). Additionally, we found that the risk of premature MI was significantly and independently increased in definite/probable FH patients (OR=5.32, 95%CI 2.77-10.22, P<0.01). None of FH patients reached the target of LDL-C<1.8 mmol/L under statin therapy. Conclusions The prevalence of FH in Chinese patients with MI is not rare. Clinically, FH is linked with the early onset of MI.

Objective To study the relationship of different ABO blood types with the risk of cardiovascular events and the severity of CHD.Methods A total of coronary arteriography-confirmed 3823 Chinese Han CHD patients were divided into O blood type group (n=1140) and non-O blood type group (n=2683).A total of 3654 patients who were followed up by telephone for a median period of 24.6 months were divided into cardiovascular events group (n=348) and cardiovascular events-free group (n =3306).The risk of cardiovascular events in CHD patients with different ABO blood types was assessed according to the Cox proportional hazards model.Results The incidence of left main branch lesion or 3-branch lesions was significantly higher in cardiovascular events group than in cardiovascular events-free group (15.2％ vs 8.1％,47.7％ vs 30.5％,P＜0.01).The Gensini score was significantly higher in non-O blood type group than in O blood type group (20 vs 18,P＜0.05).The incidence of cardiovascular events was higher in non-O blood type group than in O blood type group (10.3％ vs 7.8％,P=0.019).Cox proportional hazards model showed that non-O blood type was an risk factor for cardiovascular events (HR =1.318,95 ％CI:1.030-1.685).The risk of cardiovascular events was still higher in non-O blood type group than in O blood type group after adjustment for confounders (HR=1.291,95％CI:1.008-1.657,P=0.046).Conclusion Non-O blood type is closely related with cardiovascular events in Chinese Han CHD patients.

Objective To investigate the efficacy of pretreatment systemic inflammation response index (SIRI) in predicting the prognostic of prostate cancer (PCa) patients treated with maximal androgen blockade (MAB).Methods The data of 351 PCa patients who had undergone MAB as first-line therapy between January 2010 and June 2015,were retrospectively analyzed.The age of patients in our cohort ranged from 51 to 89 years old,mean 76 years old.The median value of PSA was 91.60ng/ml,ranging 0.11-1 000.00 ng/ml.39 cases had a Gleason score of 6,47 cases had a score of 3 + 4,89 cases had a score of 4 +3,107 cases had a score of 8,and 69 cases had a score of 9-10.158 cases had bone metastasis.Patients were categorized in two groups using a cut-off point of 1.2 as calculated by the receiver-operating curve analysis.Correlations between SIRI and clinical characteristics were analyzed.Meanwhile,univariate and multivariate cox regression analyses were performed to determine the associations of SIRI with progression-free survival (PFS),cancer-specific survival (CSS) and overall survival (OS).Results The median follow-up duration was 43.0 months,ranging 9-75 months.The disease progression occurred in 162 patients,91 patients died,including 75 who died because of PCa at the end of the last follow-up.The differences of age,Gleason score and incidence of metastasis between low SIRI group (＜ 1.2) and high SIRI group (≥1.2) were not significant (P ＞0.05).But the patients in high SIRI group had higher PSA (P =0.046).Multivariate analyses identified SIRI,Gleason score and metastasis as independent prognostic factors for PFS,CSS and OS.Conclusions Pretreatment SIRI ≥ 1.2 was an independent predictor for poor prognosis in PCa patients treated with MAB.